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

Pharmacokinetics of Mycophenolate Mofetil in de Novo Lung Allograft Recipients

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01014442

Enrollment

Registered

2009-11-17

Start date

2010-01-31

Completion date

2012-06-30

Last updated

2017-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Transplantation

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.

Interventions

DRUGmycophenolate mofetil

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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%.
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 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 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 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%.
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%.
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.
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).
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.
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 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.
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.
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.
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.
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	Predose (0 hour) on Day 4 post-transplantation	Cmin was expressed in mg/L.
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 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.
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 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.
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.
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.
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.
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.
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).
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.
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\*\[mg/L\]).
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 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).
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).
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).
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).
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).
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.

Secondary

Measure	Time frame	Description
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%
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.
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.
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.
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.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
MMF - Cystic Fibrosis Participants with cystic fibrosis having transplantation at Day 0, received MMF capsules at dose of 1.5 g BID from Day 2 to Day 30 post-transplantation and then at 1 g BID from Day 31 to Day 90 post-transplantation.	33
MMF - COPD, Emphysema, IPF, or A1AD Participants with COPD, emphysema, IPF or A1AD having transplantation at Day 0, received MMF capsules at dose of 1.5 g BID from Day 2 to Day 30 post-transplantation and then at 1 g BID from Day 31 to Day 90 post-transplantation.	35
Total	68

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	8
Overall Study	Lack of Compliance	0	1
Overall Study	Protocol Violation	2	5
Overall Study	Unspecified Reason	1	1
Overall Study	Withdrawal by Subject	4	4

Baseline characteristics

Characteristic	MMF - Cystic Fibrosis	MMF - COPD, Emphysema, IPF, or A1AD	Total
Age, Continuous	31.3 years STANDARD_DEVIATION 7.42	54.3 years STANDARD_DEVIATION 7.93	43.1 years STANDARD_DEVIATION 13.86
Gender Female	13 Participants	14 Participants	27 Participants
Gender Male	20 Participants	21 Participants	41 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	27 / 33	29 / 35
serious Total, serious adverse events	13 / 33	14 / 35

Outcome results

Primary

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\*\[mg/L\]).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	MPA	23.460 hours*(mg/L)	Standard Deviation 7.8103
MMF - Cystic Fibrosis	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	MPAG	1095.98 hours*(mg/L)	Standard Deviation 659.211
MMF - Cystic Fibrosis	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	10.414 hours*(mg/L)	Standard Deviation 7.5535
MMF - COPD, Emphysema, IPF, or A1AD	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	MPA	27.174 hours*(mg/L)	Standard Deviation 10.4909
MMF - COPD, Emphysema, IPF, or A1AD	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	MPAG	829.14 hours*(mg/L)	Standard Deviation 281.878
MMF - COPD, Emphysema, IPF, or A1AD	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	13.672 hours*(mg/L)	Standard Deviation 6.6349

Comparison: AUC0-12 of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.279895% CI: [-8.5642, 3.0044]Wilcoxon rank sum test

Comparison: AUC0-12 of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.406395% CI: [-107.1596, 393.5295]Wilcoxon rank sum test

Comparison: AUC0-12 of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.044195% CI: [-8.1854, -0.1887]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of Free MPA at Day 20	48.530 hours*mcg/L	Standard Deviation 30.3408
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of Free MPA at Day 20	89.315 hours*mcg/L	Standard Deviation 90.3819

Comparison: Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.067295% CI: [-44.8217, 3.7573]Wilcoxon rank sum test

Primary

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\*\[mcg/L\]).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of Free MPA at Day 4	135.703 hours*mcg/L	Standard Deviation 120.4152
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of Free MPA at Day 4	80.272 hours*mcg/L	Standard Deviation 45.9523

Comparison: Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.234295% CI: [-16.0292, 79.365]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of Free MPA at Day 8	61.155 hours*mcg/L	Standard Deviation 26.0913
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of Free MPA at Day 8	83.683 hours*mcg/L	Standard Deviation 51.4228

Comparison: Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.196495% CI: [-37.395, 5.4825]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of Free MPA at Day 90	68.874 hours*mcg/L	Standard Deviation 64.6536
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of Free MPA at Day 90	99.212 hours*mcg/L	Standard Deviation 81.0812

Comparison: Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.245395% CI: [-64.1567, 8.5708]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	MPA	18.925 hours*(mg/L)	Standard Deviation 10.7674
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	MPAG	812.65 hours*(mg/L)	Standard Deviation 391.881
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	AcMPAG	3.252 hours*(mg/L)	Standard Deviation 2.2066
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	MPA	28.290 hours*(mg/L)	Standard Deviation 10.5485
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	MPAG	1095.37 hours*(mg/L)	Standard Deviation 391.62
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 20	AcMPAG	9.482 hours*(mg/L)	Standard Deviation 6.6815

Comparison: AUC0-12 of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.000295% CI: [-13.7713, -4.6498]Wilcoxon rank sum test

Comparison: AUC0-12 of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.005895% CI: [-506.7782, -77.397]Wilcoxon rank sum test

Comparison: AUC0-12 of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: <0.000195% CI: [-7.1455, -2.6133]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	MPAG	881.50 hours*(mg/L)	Standard Deviation 634.587
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	MPA	17.841 hours*(mg/L)	Standard Deviation 8.2077
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	AcMPAG	6.064 hours*(mg/L)	Standard Deviation 4.2591
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	MPA	23.352 hours*(mg/L)	Standard Deviation 10.7853
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	MPAG	888.96 hours*(mg/L)	Standard Deviation 277.565
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 8	AcMPAG	9.081 hours*(mg/L)	Standard Deviation 6.5063

Comparison: AUC0-12 of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.05195% CI: [-11.7302, 0.0033]Wilcoxon rank sum test

Comparison: AUC0-12 of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.273395% CI: [-361.4437, 171.9652]Wilcoxon rank sum test

Comparison: AUC0-12 of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.071895% CI: [-4.8456, 0.2067]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure. Number of participants with available data for specified category are provided against individual category.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	MPA	32.365 hours*(mg/L)	Standard Deviation 16.4658
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	MPAG	776.28 hours*(mg/L)	Standard Deviation 385.31
MMF - Cystic Fibrosis	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	AcMPAG	7.776 hours*(mg/L)	Standard Deviation 5.0791
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	MPA	31.864 hours*(mg/L)	Standard Deviation 15.5442
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	MPAG	972.69 hours*(mg/L)	Standard Deviation 530.667
MMF - COPD, Emphysema, IPF, or A1AD	AUC0-12 of MPA, MPAG and AcMPAG at Day 90	AcMPAG	7.219 hours*(mg/L)	Standard Deviation 5.2217

Comparison: AUC0-12 of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.714495% CI: [-12.101, 14.6563]Wilcoxon rank sum test

Comparison: AUC0-12 of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.341395% CI: [-526.0765, 195.8348]Wilcoxon rank sum test

Comparison: AUC0-12 of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.625195% CI: [-3.0288, 4.2273]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	MPA	68.471 L/hours	Standard Deviation 32.7611
MMF - Cystic Fibrosis	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	MPAG	1.6754 L/hours	Standard Deviation 0.8191
MMF - Cystic Fibrosis	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	206.60 L/hours	Standard Deviation 151.301
MMF - COPD, Emphysema, IPF, or A1AD	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	MPA	56.709 L/hours	Standard Deviation 22.3503
MMF - COPD, Emphysema, IPF, or A1AD	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	MPAG	1.7615 L/hours	Standard Deviation 0.46573
MMF - COPD, Emphysema, IPF, or A1AD	Clearance (CL) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	140.96 L/hours	Standard Deviation 110.4

Comparison: CL of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.136295% CI: [-3.911, 18.4444]Wilcoxon rank sum test

Comparison: CL of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.432595% CI: [-0.5693, 0.271]Wilcoxon rank sum test

Comparison: CL of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.031695% CI: [4.197, 112.7806]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 20	MPA	83.068 L/hour	Standard Deviation 27.7321
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 20	MPAG	1.9338 L/hour	Standard Deviation 0.69979
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 20	AcMPAG	680.68 L/hour	Standard Deviation 614.97
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 20	MPA	58.295 L/hour	Standard Deviation 19.58
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 20	MPAG	1.4788 L/hour	Standard Deviation 0.44488
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 20	AcMPAG	232.34 L/hour	Standard Deviation 179.449

Comparison: CL of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.004895% CI: [8.2373, 43.5102]Wilcoxon rank sum test

Comparison: CL of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.027795% CI: [0.034, 0.9925]Wilcoxon rank sum test

Comparison: CL of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.000295% CI: [154.1902, 526.1716]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 8	MPA	90.921 L/hour	Standard Deviation 33.7184
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 8	MPAG	2.3235 L/hour	Standard Deviation 1.55336
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 8	AcMPAG	410.86 L/hour	Standard Deviation 448.947
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 8	MPA	81.578 L/hour	Standard Deviation 63.7936
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 8	MPAG	1.7847 L/hour	Standard Deviation 0.75624
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 8	AcMPAG	253.81 L/hour	Standard Deviation 237.283

Comparison: CL of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.057295% CI: [-0.425, 35.3852]Wilcoxon rank sum test

Comparison: CL of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.319895% CI: [-0.2524, 1.1097]Wilcoxon rank sum test

Comparison: CL of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.084595% CI: [-6.7706, 160.3469]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 90	MPA	38.091 L/hour	Standard Deviation 20.9125
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 90	MPAG	1.5701 L/hour	Standard Deviation 0.99265
MMF - Cystic Fibrosis	CL of MPA, MPAG and AcMPAG at Day 90	AcMPAG	231.28 L/hour	Standard Deviation 218.455
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 90	MPA	36.922 L/hour	Standard Deviation 15.2129
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 90	MPAG	1.2433 L/hour	Standard Deviation 0.53337
MMF - COPD, Emphysema, IPF, or A1AD	CL of MPA, MPAG and AcMPAG at Day 90	AcMPAG	223.56 L/hour	Standard Deviation 191.887

Comparison: CL of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.941795% CI: [-14.5052, 11.6346]Wilcoxon rank sum test

Comparison: CL of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.294195% CI: [-0.1954, 0.6246]Wilcoxon rank sum test

Comparison: CL of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.81795% CI: [-84.8234, 109.9321]Wilcoxon rank sum test

Primary

Cmax of Free MPA at Day 20

Cmax was expressed in mcg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of Free MPA at Day 20	51.822 mcg/L	Standard Deviation 39.9533
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of Free MPA at Day 20	100.094 mcg/L	Standard Deviation 120.8269

Comparison: Cmax of Free MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.115195% CI: [-52.27, 5.97]Wilcoxon rank sum test

Primary

Cmax of Free MPA at Day 4

Cmax was expressed in micrograms per liter (mcg/L).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of Free MPA at Day 4	135.275 mcg/L	Standard Deviation 133.2231
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of Free MPA at Day 4	84.014 mcg/L	Standard Deviation 57.8348

Comparison: Cmax of Free MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.300295% CI: [-16.5, 74.32]Wilcoxon rank sum test

Primary

Cmax of Free MPA at Day 8

Cmax was expressed in mcg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of Free MPA at Day 8	59.571 mcg/L	Standard Deviation 35.1104
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of Free MPA at Day 8	95.553 mcg/L	Standard Deviation 62.6051

Comparison: Cmax of Free MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.033495% CI: [-53.25, -2.29]Wilcoxon rank sum test

Primary

Cmax of Free MPA at Day 90

Cmax was expressed in mcg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of Free MPA at Day 90	87.293 mcg/L	Standard Deviation 97.6509
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of Free MPA at Day 90	101.472 mcg/L	Standard Deviation 93.9834

Comparison: Cmax of Free MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.597495% CI: [-63.88, 30.56]Wilcoxon rank sum test

Primary

Cmax of MPA, MPAG and AcMPAG at Day 20

Cmax was expressed in mg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 20	MPA	5.284 mg/L	Standard Deviation 3.8472
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 20	MPAG	93.882 mg/L	Standard Deviation 37.6112
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 20	AcMPAG	0.624 mg/L	Standard Deviation 0.3895
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 20	MPA	6.762 mg/L	Standard Deviation 3.7405
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 20	MPAG	124.450 mg/L	Standard Deviation 45.0613
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 20	AcMPAG	1.434 mg/L	Standard Deviation 1.0501

Comparison: Cmax of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.000895% CI: [-1.02, -0.27]Wilcoxon rank sum test

Comparison: Cmax of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.088695% CI: [-3.79, 0.28]Wilcoxon rank sum test

Comparison: Cmax of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.02295% CI: [-54.97, -6.36]Wilcoxon rank sum test

Primary

Cmax of MPA, MPAG and AcMPAG at Day 8

Cmax was expressed in mg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 8	MPA	5.124 mg/L	Standard Deviation 4.2748
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 8	MPAG	100.127 mg/L	Standard Deviation 54.0215
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 8	AcMPAG	1.007 mg/L	Standard Deviation 0.5914
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 8	MPA	6.106 mg/L	Standard Deviation 3.3663
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 8	MPAG	100.128 mg/L	Standard Deviation 25.1228
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 8	AcMPAG	1.361 mg/L	Standard Deviation 0.9163

Comparison: Cmax of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.130895% CI: [-2.99, 0.41]Wilcoxon rank sum test

Comparison: Cmax of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.488695% CI: [-31.5, 20.79]Wilcoxon rank sum test

Comparison: Cmax of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.221895% CI: [-0.6, 0.19]Wilcoxon rank sum test

Primary

Cmax of MPA, MPAG and AcMPAG at Day 90

Cmax was expressed in mg/L.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 90	MPA	12.915 mg/L	Standard Deviation 9.2479
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 90	MPAG	104.938 mg/L	Standard Deviation 44.6135
MMF - Cystic Fibrosis	Cmax of MPA, MPAG and AcMPAG at Day 90	AcMPAG	1.375 mg/L	Standard Deviation 0.6514
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 90	MPA	7.294 mg/L	Standard Deviation 3.1817
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 90	MPAG	113.453 mg/L	Standard Deviation 48.2935
MMF - COPD, Emphysema, IPF, or A1AD	Cmax of MPA, MPAG and AcMPAG at Day 90	AcMPAG	1.163 mg/L	Standard Deviation 0.6856

Comparison: Cmax of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.031895% CI: [0.25, 8.23]Wilcoxon rank sum test

Comparison: Cmax of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.714495% CI: [-51.19, 30.7]Wilcoxon rank sum test

Comparison: Cmax of AcMPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.39395% CI: [-0.31, 0.88]Wilcoxon rank sum test

Primary

Cmin of Free MPA at Day 20

Cmin was expressed in mcg/L.

Time frame: Predose (0 hour) on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of Free MPA at Day 20	12.193 mcg/L	Standard Deviation 9.1443
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of Free MPA at Day 20	20.237 mcg/L	Standard Deviation 16.2117

Primary

Cmin of Free MPA at Day 4

Cmin was expressed in mcg/L.

Time frame: Predose (0 hour) on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of Free MPA at Day 4	40.188 mcg/L	Standard Deviation 37.9357
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of Free MPA at Day 4	23.711 mcg/L	Standard Deviation 14.6991

Primary

Cmin of Free MPA at Day 8

Cmin was expressed in mcg/L.

Time frame: Predose (0 hour) on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of Free MPA at Day 8	18.161 mcg/L	Standard Deviation 16.3831
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of Free MPA at Day 8	15.669 mcg/L	Standard Deviation 9.6168

Primary

Cmin of Free MPA at Day 90

Cmin was expressed in mcg/L.

Time frame: Predose (0 hour) on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of Free MPA at Day 90	8.102 mcg/L	Standard Deviation 3.3201
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of Free MPA at Day 90	18.831 mcg/L	Standard Deviation 12.6155

Primary

Cmin of MPA, MPAG and AcMPAG at Day 20

Cmin was expressed in mg/L.

Time frame: Predose (0 hour) on Day 20 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 20	MPA	0.782 mg/L	Standard Deviation 0.5945
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 20	MPAG	58.484 mg/L	Standard Deviation 29.5576
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 20	AcMPAG	0.261 mg/L	Standard Deviation 0.1662
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 20	MPA	1.234 mg/L	Standard Deviation 0.9971
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 20	MPAG	69.023 mg/L	Standard Deviation 25.6603
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 20	AcMPAG	0.528 mg/L	Standard Deviation 0.3977

Comparison: Cmin of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.081895% CI: [-0.56, 0.05]Wilcoxon rank sum test

Comparison: Cmin of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.094595% CI: [-26.9, 2.94]Wilcoxon rank sum test

Comparison: Cmin of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.008195% CI: [-0.41, -0.04]Wilcoxon rank sum test

Primary

Cmin of MPA, MPAG and AcMPAG at Day 8

Cmin was expressed in mg/L.

Time frame: Predose (0 hour) on Day 8 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 8	MPA	0.750 mg/L	Standard Deviation 0.6136
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 8	MPAG	54.566 mg/L	Standard Deviation 51.2379
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 8	AcMPAG	0.386 mg/L	Standard Deviation 0.487
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 8	MPA	0.772 mg/L	Standard Deviation 0.3482
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 8	MPAG	57.189 mg/L	Standard Deviation 20.8518
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 8	AcMPAG	0.517 mg/L	Standard Deviation 0.2623

Comparison: Cmin of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.402795% CI: [-0.38, 0.19]Wilcoxon rank sum test

Comparison: Cmin of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.087595% CI: [-29.35, 6.39]Wilcoxon rank sum test

Comparison: Cmin of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.011295% CI: [-0.35, -0.05]Wilcoxon rank sum test

Primary

Cmin of MPA, MPAG and AcMPAG at Day 90

Cmin was expressed in mg/L.

Time frame: Predose (0 hour) on Day 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 90	MPA	1.103 mg/L	Standard Deviation 0.7446
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 90	MPAG	57.957 mg/L	Standard Deviation 32.6863
MMF - Cystic Fibrosis	Cmin of MPA, MPAG and AcMPAG at Day 90	AcMPAG	0.449 mg/L	Standard Deviation 0.3552
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 90	MPA	1.570 mg/L	Standard Deviation 1.0282
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 90	MPAG	80.488 mg/L	Standard Deviation 37.2631
MMF - COPD, Emphysema, IPF, or A1AD	Cmin of MPA, MPAG and AcMPAG at Day 90	AcMPAG	0.466 mg/L	Standard Deviation 0.3096

Comparison: Cmin of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.328995% CI: [-1.14, 0.28]Wilcoxon rank sum test

Comparison: Cmin of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.124395% CI: [-49.39, 4.71]Wilcoxon rank sum test

Comparison: Cmin of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.870495% CI: [-0.28, 0.23]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	0.01402 hours/L	Standard Deviation 0.007208
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	0.6059 hours/L	Standard Deviation 0.28149
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	0.00239 hours/L	Standard Deviation 0.001707
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MPA	0.0000399 hours/L	Standard Deviation 0.00003632
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MPA	0.0000597 hours/L	Standard Deviation 0.0000602
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	0.01923 hours/L	Standard Deviation 0.007029
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	0.00642 hours/L	Standard Deviation 0.004432
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	0.7440 hours/L	Standard Deviation 0.26032

Comparison: Dose-Normalized AUC0-12 of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.004895% CI: [-0.00876, -0.00148]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.027795% CI: [-0.31026, -0.01067]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.000295% CI: [-0.00476, 0.00168]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of Free MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.166195% CI: [-0.0000295, 0.0000047]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	0.01652 hours/L	Standard Deviation 0.004684
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	0.7720 hours/L	Standard Deviation 0.42519
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	0.00739 hours/L	Standard Deviation 0.005002
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	0.0000943 hours/L	Standard Deviation 0.00008029
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	0.0000594 hours/L	Standard Deviation 0.00003237
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	0.02016 hours/L	Standard Deviation 0.007383
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	0.01056 hours/L	Standard Deviation 0.005828
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	0.6165 hours/L	Standard Deviation 0.20281

Comparison: Dose-Normalized AUC0-12 of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.136295% CI: [-0.00734, 0.00106]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.432595% CI: [-0.08467, 0.26322]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.031695% CI: [-0.00645, -0.00029]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of Free MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.326995% CI: [-0.0000134, 0.0000552]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	0.01256 hours/L	Standard Deviation 0.005018
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	0.6157 hours/L	Standard Deviation 0.40835
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPAG	0.00426 hours/L	Standard Deviation 0.002733
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	0.0000428 hours/L	Standard Deviation 0.00001807
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	0.0000580 hours/L	Standard Deviation 0.0000333
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	0.01624 hours/L	Standard Deviation 0.007077
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPAG	0.00644 hours/L	Standard Deviation 0.004471
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	0.6270 hours/L	Standard Deviation 0.18884

Comparison: Dose-Normalized AUC0-12 of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.057295% CI: [-0.00761, 0.0001]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.319895% CI: [-0.25269, 0.11464]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.084595% CI: [-0.00352, 0.00013]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of Free MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.176995% CI: [-0.000025, 0.0000043]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	0.03126 hours/L	Standard Deviation 0.011529
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	0.7887 hours/L	Standard Deviation 0.31007
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	0.00748 hours/L	Standard Deviation 0.004735
MMF - Cystic Fibrosis	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	0.0000752 hours/L	Standard Deviation 0.00006364
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	0.00001023 hours/L	Standard Deviation 0.00007888
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	0.03172 hours/L	Standard Deviation 0.012879
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	0.00700 hours/L	Standard Deviation 0.004084
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	0.9190 hours/L	Standard Deviation 0.31896

Comparison: Dose-Normalized AUC0-12 of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.941795% CI: [-0.01037, 0.01042]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.294195% CI: [-0.39951, 0.12988]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.81795% CI: [-0.00361, 0.00421]Wilcoxon rank sum test

Comparison: Dose-Normalized AUC0-12 of Free MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.192795% CI: [-0.0000594, 0.0000154]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	0.00395 1/L	Standard Deviation 0.002619
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	0.07044 1/L	Standard Deviation 0.029284
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	0.000482 1/L	Standard Deviation 0.0003487
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MP	0.0000439 1/L	Standard Deviation 0.0000475
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MP	0.0000666 1/L	Standard Deviation 0.00008052
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	0.00456 1/L	Standard Deviation 0.002462
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	0.000969 1/L	Standard Deviation 0.0006947
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	0.08430 1/L	Standard Deviation 0.02943

Comparison: Dose-Normalized Cmax of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.378495% CI: [-0.0023, 0.00084]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.094295% CI: [-0.03229, 0.00297]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.003295% CI: [-0.00062, -0.00015]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of Free MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.17695% CI: [-0.0000328, -0.0000091]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	0.00557 1/L	Standard Deviation 0.003907
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	0.08286 1/L	Standard Deviation 0.037461
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	0.001122 1/L	Standard Deviation 0.000635
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	0.0000929 1/L	Standard Deviation 0.00008796
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	0.0000625 1/L	Standard Deviation 0.00003907
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	0.00422 1/L	Standard Deviation 0.001924
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	0.001388 1/L	Standard Deviation 0.000716
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	0.06749 1/L	Standard Deviation 0.017478

Comparison: Dose-Normalized Cmax of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.546695% CI: [-0.00103, 0.00259]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.322395% CI: [-0.00707, 0.03161]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.210895% CI: [-0.0007, 0.00012]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of Free MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called a Hodges-Lehmann estimator.p-value: 0.433495% CI: [-0.000014, 0.0000462]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	0.00356 1/L	Standard Deviation 0.002769
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	0.06980 1/L	Standard Deviation 0.033524
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPA	0.000702 1/L	Standard Deviation 0.0003736
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	0.0000409 1/L	Standard Deviation 0.00002274
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	0.0000663 1/L	Standard Deviation 0.00004075
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	0.00435 1/L	Standard Deviation 0.002522
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPA	0.000967 1/L	Standard Deviation 0.0006297
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	0.07070 1/L	Standard Deviation 0.017856

Comparison: Dose-Normalized Cmax of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.151195% CI: [-0.00216, 0.0003]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.413195% CI: [-0.0205, 0.01103]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.267795% CI: [-0.00046, 0.00013]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of Free MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.017395% CI: [-0.0000394, -0.000005]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	0.01261 1/L	Standard Deviation 0.007644
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	0.10671 1/L	Standard Deviation 0.037035
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	0.001377 1/L	Standard Deviation 0.0006935
MMF - Cystic Fibrosis	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	0.0000945 1/L	Standard Deviation 0.0000964
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	0.0001043 1/L	Standard Deviation 0.00009208
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	0.00742 1/L	Standard Deviation 0.003631
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	0.001134 1/L	Standard Deviation 0.00051
MMF - COPD, Emphysema, IPF, or A1AD	Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	0.10948 1/L	Standard Deviation 0.030395

Comparison: Dose-Normalized Cmax of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.050995% CI: [-0.00027, 0.00833]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.826295% CI: [-0.03414, 0.02671]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.434595% CI: [-0.0003, 0.0007]Wilcoxon rank sum test

Comparison: Dose-Normalized Cmax of Free MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.647295% CI: [-0.0000586, 0.0000364]Wilcoxon rank sum test

Primary

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%.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Free Fraction of Free MPA at Day 20	0.2922 percentage of free fraction	Standard Deviation 0.19811
MMF - COPD, Emphysema, IPF, or A1AD	Free Fraction of Free MPA at Day 20	0.3052 percentage of free fraction	Standard Deviation 0.22218

Comparison: Free Fraction of Free MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.987395% CI: [-0.1152, 0.1173]Wilcoxon rank sum test

Primary

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%.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Free Fraction of Free MPA at Day 4	0.5789 percentage of free fraction	Standard Deviation 0.42113
MMF - COPD, Emphysema, IPF, or A1AD	Free Fraction of Free MPA at Day 4	0.3208 percentage of free fraction	Standard Deviation 0.16486

Comparison: Free Fraction of Free MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.082195% CI: [-0.0121, 0.4188]Wilcoxon rank sum test

Primary

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%.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Free Fraction of Free MPA at Day 8	0.3595 percentage of free fraction	Standard Deviation 0.13517
MMF - COPD, Emphysema, IPF, or A1AD	Free Fraction of Free MPA at Day 8	0.3594 percentage of free fraction	Standard Deviation 0.20504

Comparison: Free Fraction of Free MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.362895% CI: [-0.0455, 0.1221]Wilcoxon rank sum test

Primary

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%.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Population: PP Population. Here, number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Free Fraction of Free MPA at Day 90	0.2270 percentage of free fraction	Standard Deviation 0.14614
MMF - COPD, Emphysema, IPF, or A1AD	Free Fraction of Free MPA at Day 90	0.3020 percentage of free fraction	Standard Deviation 0.13446

Comparison: Free Fraction of Free MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.217895% CI: [-0.187, 0.0265]Wilcoxon rank sum test

Primary

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).

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 after transplantation

Population: Per Protocol (PP) Population: Intent-to treat (ITT) population (received at least one dose of study drug and where the primary variable was measured at least once under study drug) excluding participants with major protocol violations (total 46 participants). Number of participants analyzed=participants who were evaluable for this outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	MPA	7.914 mg/L	Standard Deviation 5.4645
MMF - Cystic Fibrosis	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	MPAG	117.210 mg/L	Standard Deviation 58.9632
MMF - Cystic Fibrosis	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	AcMPAG	1.583 mg/L	Standard Deviation 0.9697
MMF - COPD, Emphysema, IPF, or A1AD	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	MPA	5.608 mg/L	Standard Deviation 2.5591
MMF - COPD, Emphysema, IPF, or A1AD	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	MPAG	91.207 mg/L	Standard Deviation 26.3876
MMF - COPD, Emphysema, IPF, or A1AD	Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4	AcMPAG	1.810 mg/L	Standard Deviation 0.8306

Comparison: Cmax of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.264995% CI: [-0.83, 4.25]Wilcoxon rank sum test

Comparison: Cmax of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.311395% CI: [-10.2, 42.78]Wilcoxon rank sum test

Comparison: Cmax of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.295395% CI: [-0.81, 0.19]Wilcoxon rank sum test

Primary

Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4

Cmin was expressed in mg/L.

Time frame: Predose (0 hour) on Day 4 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	MPA	1.267 mg/L	Standard Deviation 1.0082
MMF - Cystic Fibrosis	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	MPAG	66.917 mg/L	Standard Deviation 41.3384
MMF - Cystic Fibrosis	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	0.602 mg/L	Standard Deviation 0.5628
MMF - COPD, Emphysema, IPF, or A1AD	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	MPA	1.094 mg/L	Standard Deviation 0.8473
MMF - COPD, Emphysema, IPF, or A1AD	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	MPAG	47.493 mg/L	Standard Deviation 17.9747
MMF - COPD, Emphysema, IPF, or A1AD	Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	0.733 mg/L	Standard Deviation 0.4686

Comparison: Cmin of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.522495% CI: [-0.26, 0.5]Wilcoxon rank sum test

Comparison: Cmin of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.208895% CI: [-5.29, 30.29]Wilcoxon rank sum test

Comparison: Cmin of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.179495% CI: [-0.45, 0.08]Wilcoxon rank sum test

Primary

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

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	1.823 hour	Standard Deviation 1.1626
MMF - Cystic Fibrosis	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	3.713 hour	Standard Deviation 2.4167
MMF - Cystic Fibrosis	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	2.379 hour	Standard Deviation 1.2344
MMF - Cystic Fibrosis	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	1.472 hour	Standard Deviation 0.3758
MMF - COPD, Emphysema, IPF, or A1AD	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	Free MPA	1.405 hour	Standard Deviation 0.4644
MMF - COPD, Emphysema, IPF, or A1AD	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPA	2.892 hour	Standard Deviation 2.9202
MMF - COPD, Emphysema, IPF, or A1AD	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	AcMPAG	3.405 hour	Standard Deviation 1.9162
MMF - COPD, Emphysema, IPF, or A1AD	Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4	MPAG	4.891 hour	Standard Deviation 2.6546

Comparison: Tmax of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.574595% CI: [-1.95, 0.5]Wilcoxon rank sum test

Comparison: Tmax of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.200395% CI: [-2.3333, 0.0833]Wilcoxon rank sum test

Comparison: Tmax of AcMPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.092995% CI: [-2.0833, 0]Wilcoxon rank sum test

Comparison: Tmax of Free MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.082395% CI: [0, 0.0667]Wilcoxon rank sum test

Primary

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

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	2.293 hour	Standard Deviation 1.9048
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	3.762 hour	Standard Deviation 2.2954
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	2.842 hour	Standard Deviation 1.7915
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MPA	1.236 hour	Standard Deviation 0.6144
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	Free MPA	1.366 hour	Standard Deviation 0.4692
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPA	2.463 hour	Standard Deviation 1.8928
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	AcMPAG	3.411 hour	Standard Deviation 1.8799
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20	MPAG	4.907 hour	Standard Deviation 2.8568

Comparison: Tmax of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 195% CI: [-1.1667, 0.5833]Wilcoxon rank sum test

Comparison: Tmax of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.494795% CI: [-2, 0.0833]Wilcoxon rank sum test

Comparison: Tmax of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.442595% CI: [-1.9667, 0.2]Wilcoxon rank sum test

Comparison: Tmax of Free MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.97295% CI: [-0.05, 0.0333]Wilcoxon rank sum test

Primary

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

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	2.138 hour	Standard Deviation 1.4976
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	3.669 hour	Standard Deviation 1.4773
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPAG	2.802 hour	Standard Deviation 1.2418
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	1.272 hour	Standard Deviation 0.5982
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	Free MPA	1.446 hour	Standard Deviation 0.3638
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPA	1.659 hour	Standard Deviation 0.953
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	AcMPAG	2.546 hour	Standard Deviation 1.1508
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8	MPAG	3.647 hour	Standard Deviation 1.4555

Comparison: Tmax of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.810695% CI: [-0.5, 1.7333]Wilcoxon rank sum test

Comparison: Tmax of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 195% CI: [-0.1667, 0.1667]Wilcoxon rank sum test

Comparison: Tmax of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.631195% CI: [-0.3333, 1.4667]Wilcoxon rank sum test

Comparison: Tmax of Free MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.43395% CI: [-0.1667, 0.0167]Wilcoxon rank sum test

Primary

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

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	1.450 hour	Standard Deviation 0.5251
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	3.095 hour	Standard Deviation 1.7884
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	2.234 hour	Standard Deviation 1.0899
MMF - Cystic Fibrosis	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	1.490 hour	Standard Deviation 0.0666
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	Free MPA	1.485 hour	Standard Deviation 0.5282
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPA	2.143 hour	Standard Deviation 2.2487
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	AcMPAG	3.564 hour	Standard Deviation 2.3686
MMF - COPD, Emphysema, IPF, or A1AD	Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90	MPAG	4.420 hour	Standard Deviation 1.9078

Comparison: Tmax of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.883495% CI: [-1.1667, 0.7]Wilcoxon rank sum test

Comparison: Tmax of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.038695% CI: [-2.2, 0]Wilcoxon rank sum test

Comparison: Tmax of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.055895% CI: [-2.6167, 0]Wilcoxon rank sum test

Comparison: Tmax of Free MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.008295% CI: [-0.2333, -0.0667]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 4 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	MPA	345.46 Liter	Standard Deviation 182.247
MMF - Cystic Fibrosis	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	MPAG	11.681 Liter	Standard Deviation 4.7587
MMF - Cystic Fibrosis	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	1065.02 Liter	Standard Deviation 611.137
MMF - COPD, Emphysema, IPF, or A1AD	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	MPA	287.74 Liter	Standard Deviation 237.295
MMF - COPD, Emphysema, IPF, or A1AD	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	MPAG	12.062 Liter	Standard Deviation 3.7316
MMF - COPD, Emphysema, IPF, or A1AD	Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4	AcMPAG	705.38 Liter	Standard Deviation 502.996

Comparison: Vz of MPA at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.155295% CI: [-23.4659, 162.9545]Wilcoxon rank sum test

Comparison: Vz of MPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.605795% CI: [-3.2675, 2.5529]Wilcoxon rank sum test

Comparison: Vz of AcMPAG at Day 4. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.018895% CI: [79.5869, 695.1789]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 20 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 20	MPA	476.06 Liter	Standard Deviation 267.025
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 20	MPAG	12.798 Liter	Standard Deviation 5.1535
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 20	AcMPAG	3006.18 Liter	Standard Deviation 2570.205
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 20	MPA	257.57 Liter	Standard Deviation 126.679
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 20	MPAG	9.533 Liter	Standard Deviation 3.1984
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 20	AcMPAG	1571.93 Liter	Standard Deviation 1944.621

Comparison: Vz of MPA at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.00495% CI: [71.2442, 355.1739]Wilcoxon rank sum test

Comparison: Vz of MPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.068995% CI: [-0.1999, 6.7766]Wilcoxon rank sum test

Comparison: Vz of AcMPAG at Day 20. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.030695% CI: [49.4696, 2793.7642]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 8 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 8	MPA	465.45 Liter	Standard Deviation 260.837
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 8	MPAG	12.168 Liter	Standard Deviation 5.1048
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 8	AcMPAG	1432.88 Liter	Standard Deviation 919.423
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 8	MPA	331.51 Liter	Standard Deviation 150.037
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 8	MPAG	12.740 Liter	Standard Deviation 5.2593
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 8	AcMPAG	1173.38 Liter	Standard Deviation 708.767

Comparison: Vz of MPA at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.065995% CI: [-5.7876, 209.0183]Wilcoxon rank sum test

Comparison: Vz of MPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.784295% CI: [-3.1366, 2.292]Wilcoxon rank sum test

Comparison: Vz of AcMPAG at Day 8. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.407295% CI: [-233.6483, 560.0069]Wilcoxon rank sum test

Primary

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.

Time frame: Predose (0 hour), 0.5, 1, 1.5, 2, 4, 8, 10, and 12 hours post-dose on Day 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 90	MPA	139.48 Liter	Standard Deviation 78.679
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 90	MPAG	9.254 Liter	Standard Deviation 4.6738
MMF - Cystic Fibrosis	Vz of MPA, MPAG and AcMPAG at Day 90	AcMPAG	811.15 Liter	Standard Deviation 404.733
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 90	MPA	192.53 Liter	Standard Deviation 226.826
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 90	MPAG	9.201 Liter	Standard Deviation 4.4274
MMF - COPD, Emphysema, IPF, or A1AD	Vz of MPA, MPAG and AcMPAG at Day 90	AcMPAG	980.49 Liter	Standard Deviation 473.444

Comparison: Vz of MPA at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.902995% CI: [-73.5212, 59.8304]Wilcoxon rank sum test

Comparison: Vz of MPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.969295% CI: [-3.6739, 3.9521]Wilcoxon rank sum test

Comparison: Vz of AcMPAG at Day 90. Analysis was performed using Wilcoxon rank sum test; corresponding p-value and point estimate (Hodges-Lehmann estimator) were calculated. The point estimator derived by sending the confidence level to zero is called as Hodges-Lehmann estimator.p-value: 0.374495% CI: [-644.4526, 311.9735]Wilcoxon rank sum test

Secondary

Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels

iATP was expressed in ng/mL.

Time frame: Baseline, Days 4, 8, 20 and 90 post-transplantation

Population: ITT Population. Here, number of participants analyzed = participants who were evaluable for this outcome measure. Here n= participants who were evaluable for each category, for respective arm groups.

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 4	24.0 ng/mL	Standard Deviation 223.32
MMF - Cystic Fibrosis	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 8	162.9 ng/mL	Standard Deviation 294.53
MMF - Cystic Fibrosis	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 20	-42.4 ng/mL	Standard Deviation 382.87
MMF - Cystic Fibrosis	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 90	-164.6 ng/mL	Standard Deviation 312.98
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 90	-114.7 ng/mL	Standard Deviation 138.99
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 4	85.4 ng/mL	Standard Deviation 215.78
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 20	-45.9 ng/mL	Standard Deviation 199.2
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels	Day 8	144.9 ng/mL	Standard Deviation 286.23

Secondary

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.

Time frame: Baseline, Days 20 and 90 post-transplantation

Arm	Measure	Group	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD3: Change at Day 20	-1.34 percentage of lymphocytes	Standard Deviation 13.012
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD3: Change at Day 90	1.74 percentage of lymphocytes	Standard Deviation 11.433
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD19: Change at Day 20	3.29 percentage of lymphocytes	Standard Deviation 10.554
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD19: Change at Day 90	0.59 percentage of lymphocytes	Standard Deviation 5.322
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD4: Change at Day 20	13.29 percentage of lymphocytes	Standard Deviation 15.626
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD4: Change at Day 90	9.00 percentage of lymphocytes	Standard Deviation 26.054
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD4CD25: Change at Day 20	2.72 percentage of lymphocytes	Standard Deviation 6.877
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD4CD25: Change at Day 90	0.89 percentage of lymphocytes	Standard Deviation 1.354
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD28: Change at Day 20	4.54 percentage of lymphocytes	Standard Deviation 10.105
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD28: Change at Day 90	10.15 percentage of lymphocytes	Standard Deviation 25.362
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD45RA: Change at Day 20	5.35 percentage of lymphocytes	Standard Deviation 15.802
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD45RA: Change at Day 90	-1.57 percentage of lymphocytes	Standard Deviation 12.498
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD45RO: Change at Day 20	-0.08 percentage of lymphocytes	Standard Deviation 4.199
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD45RO: Change at Day 90	-1.92 percentage of lymphocytes	Standard Deviation 7.564
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD69: Change at Day 20	5.68 percentage of lymphocytes	Standard Deviation 10.031
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD69: Change at Day 90	-0.46 percentage of lymphocytes	Standard Deviation 10.04
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD127: Change at Day 20	-1.36 percentage of lymphocytes	Standard Deviation 13.566
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD127: Change at Day 90	-0.19 percentage of lymphocytes	Standard Deviation 14.603
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD152: Change at Day 20	-3.78 percentage of lymphocytes	Standard Deviation 17.562
MMF - Cystic Fibrosis	Change From Baseline in T-Cell Phenotype	CD152: Change at Day 90	-0.28 percentage of lymphocytes	Standard Deviation 2.624
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD127: Change at Day 90	-2.03 percentage of lymphocytes	Standard Deviation 12.509
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD3: Change at Day 20	-3.01 percentage of lymphocytes	Standard Deviation 13.075
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD45RA: Change at Day 20	-5.11 percentage of lymphocytes	Standard Deviation 17.327
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD3: Change at Day 90	-2.81 percentage of lymphocytes	Standard Deviation 6.995
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD69: Change at Day 90	-0.04 percentage of lymphocytes	Standard Deviation 0.237
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD19: Change at Day 20	1.88 percentage of lymphocytes	Standard Deviation 8.046
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD45RA: Change at Day 90	-4.88 percentage of lymphocytes	Standard Deviation 13.342
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD19: Change at Day 90	0.61 percentage of lymphocytes	Standard Deviation 6
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD152: Change at Day 90	-15.59 percentage of lymphocytes	Standard Deviation 29.715
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD4: Change at Day 20	-14.71 percentage of lymphocytes	Standard Deviation 24.467
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD45RO: Change at Day 20	-2.83 percentage of lymphocytes	Standard Deviation 3.285
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD4: Change at Day 90	-1.93 percentage of lymphocytes	Standard Deviation 13.415
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD127: Change at Day 20	-3.90 percentage of lymphocytes	Standard Deviation 7.227
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD4CD25: Change at Day 20	-0.53 percentage of lymphocytes	Standard Deviation 0.94
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD45RO: Change at Day 90	-0.43 percentage of lymphocytes	Standard Deviation 7.574
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD4CD25: Change at Day 90	-0.10 percentage of lymphocytes	Standard Deviation 0.941
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD152: Change at Day 20	-10.97 percentage of lymphocytes	Standard Deviation 17.935
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD28: Change at Day 20	-4.44 percentage of lymphocytes	Standard Deviation 7.635
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD69: Change at Day 20	0.01 percentage of lymphocytes	Standard Deviation 0.328
MMF - COPD, Emphysema, IPF, or A1AD	Change From Baseline in T-Cell Phenotype	CD28: Change at Day 90	-1.04 percentage of lymphocytes	Standard Deviation 6.176

Secondary

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.

Time frame: Day 90 post-transplantation

Population: ITT Population (total 64 participants). Here, Number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation	3.087 L	Standard Deviation 0.9335
MMF - COPD, Emphysema, IPF, or A1AD	Forced Expiratory Volume in 1 Second (FEV1) at Day 90 Post-Transplantation	2.834 L	Standard Deviation 0.6912

Secondary

Forced Vital Capacity (FVC) at Day 90 Post-Transplantation

FVC at Day 90 post-transplantation is reported.

Time frame: Day 90 post-transplantation

Population: ITT Population. Here, Number of participants analyzed = participants evaluable for the outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Forced Vital Capacity (FVC) at Day 90 Post-Transplantation	3.445 L	Standard Deviation 0.9499
MMF - COPD, Emphysema, IPF, or A1AD	Forced Vital Capacity (FVC) at Day 90 Post-Transplantation	3.619 L	Standard Deviation 1.0388

Secondary

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.

Time frame: Up to Day 90

Population: Safety Population

Arm	Measure	Value (NUMBER)
MMF - Cystic Fibrosis	Percentage of Participants With Opportunistic Infections	18.2 percentage of participants
MMF - COPD, Emphysema, IPF, or A1AD	Percentage of Participants With Opportunistic Infections	20.0 percentage of participants

p-value: 195% CI: [-24.9, 22.1]Fisher Exact

Secondary

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%

Time frame: Day 90 post-transplantation

Population: ITT Population. Here, Number of participants analyzed = participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
MMF - Cystic Fibrosis	Percent of Predicted FEV1 at Day 90 Post-Transplantation	81.75 percentage of predicted FEV1	Standard Deviation 19.743
MMF - COPD, Emphysema, IPF, or A1AD	Percent of Predicted FEV1 at Day 90 Post-Transplantation	90.17 percentage of predicted FEV1	Standard Deviation 20.176

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of MPA, MPAG and AcMPAG at Day 4

AUC0-12 of Free MPA at Day 20

AUC0-12 of Free MPA at Day 4

AUC0-12 of Free MPA at Day 8

AUC0-12 of Free MPA at Day 90

AUC0-12 of MPA, MPAG and AcMPAG at Day 20

AUC0-12 of MPA, MPAG and AcMPAG at Day 8

AUC0-12 of MPA, MPAG and AcMPAG at Day 90

Clearance (CL) of MPA, MPAG and AcMPAG at Day 4

CL of MPA, MPAG and AcMPAG at Day 20

CL of MPA, MPAG and AcMPAG at Day 8

CL of MPA, MPAG and AcMPAG at Day 90

Cmax of Free MPA at Day 20

Cmax of Free MPA at Day 4

Cmax of Free MPA at Day 8

Cmax of Free MPA at Day 90

Cmax of MPA, MPAG and AcMPAG at Day 20

Cmax of MPA, MPAG and AcMPAG at Day 8

Cmax of MPA, MPAG and AcMPAG at Day 90

Cmin of Free MPA at Day 20

Cmin of Free MPA at Day 4

Cmin of Free MPA at Day 8

Cmin of Free MPA at Day 90

Cmin of MPA, MPAG and AcMPAG at Day 20

Cmin of MPA, MPAG and AcMPAG at Day 8

Cmin of MPA, MPAG and AcMPAG at Day 90

Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 20

Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 4

Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 8

Dose-Normalized AUC0-12 of MPA, MPAG, AcMPAG and Free MPA at Day 90

Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 20

Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 4

Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 8

Dose-Normalized Cmax of MPA, MPAG, AcMPAG and Free MPA at Day 90

Free Fraction of Free MPA at Day 20

Free Fraction of Free MPA at Day 4

Free Fraction of Free MPA at Day 8

Free Fraction of Free MPA at Day 90

Maximum Concentration (Cmax) of Mycophenolic Acid (MPA), Mycophenolic Acid Glucuronide (MPAG) and Acyl Glucuronide Metabolite of Mycophenolic Acid (AcMPAG) at Day 4

Minimum Concentration (Cmin) of MPA, MPAG and AcMPAG at Day 4

Time to Maximum Concentration (Tmax) of MPA, MPAG, AcMPAG and Free MPA at Day 4

Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 20

Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 8

Tmax of MPA, MPAG, AcMPAG and Free MPA at Day 90

Volume of Distribution (Vz) of MPA, MPAG and AcMPAG at Day 4

Vz of MPA, MPAG and AcMPAG at Day 20

Vz of MPA, MPAG and AcMPAG at Day 8

Vz of MPA, MPAG and AcMPAG at Day 90

Change From Baseline in Intracellular Adenosine-Tri-Phosphate (iATP) Levels

Change From Baseline in T-Cell Phenotype

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

Forced Vital Capacity (FVC) at Day 90 Post-Transplantation

Percentage of Participants With Opportunistic Infections

Percent of Predicted FEV1 at Day 90 Post-Transplantation