Trial Outcomes & Findings for Safety, Tolerability and Pharmacokinetics of Oral CellCept (Mycophenolate Mofetil) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids (NCT NCT02630563)

Last Updated: 2016-05-19

Results Overview

The area under the plasma concentration-time curve from time zero to twelve hours (AUC \[0-12h\]) is area under the plasma concentration-time curve from time zero through 12 hours. AUC (0-12) hours was computed using the linear trapezoidal rule. For the calculations of AUC (0-12h), concentrations below the limit of quantification were assigned a value of zero if they occurred at the beginning of a profile. When such values appeared at the end of a profile they were assigned as missing data. AUC0-12h was normalized to 600 milligram per square meter (mg/m\^2) and 1.5 gram. AUC was reported in microgram hour per milliliter (mcg\*h/mL).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months

Results posted on

2016-05-19

Participant Flow

The study was conducted between 02 May 2003 and 20 January 2005. This study was conducted at 2 sites in United States (US). Overall, 9 participants entered the study.

Thirty five participants were screened; 9 entered the study following a screening period of up to 14 days. Stable pediatric liver transplant participants who were at least 6 months post-transplant and who were receiving stable dose of Mycophenolate Mofetil (MMF) in combination with cyclosporine were enrolled into the study.

Participant milestones

Participant milestones
Measure	Drug MMF Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Overall Study STARTED	9
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Drug MMF Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Overall Study Administrative	1

Baseline Characteristics

Safety, Tolerability and Pharmacokinetics of Oral CellCept (Mycophenolate Mofetil) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Drug MMF n=9 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Age, Continuous	1.3 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months

Population: The pharmacokinetic (PK) population included all randomized and replaced participants adherent to the PK section of the protocol.

Outcome measures

Outcome measures
Measure	Drug MMF n=8 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area Normalized to 600mg/m^2	65.6 mcg*h/mL Standard Deviation 56.2
Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area Normalized to 1.5g	363 mcg*h/mL Standard Deviation 360

SECONDARY outcome

Population: The PK population included all randomized and replaced participants adherent to the PK section of the protocol

The area under the plasma concentration-time curve from time zero to twelve hours (AUC \[0-12h\]) is area under the plasma concentration-time curve from time zero through 12 hours. AUC (0-12) hours was computed using the linear trapezoidal rule. For the calculations of AUC (0-12h), concentrations below the limit of quantification were assigned a value of zero if they occurred at the beginning of a profile. When such values appeared at the end of a profile they were assigned as missing data. AUC was reported in microgram hour per milliliter (mcg\*h/mL).

Outcome measures

Outcome measures
Measure	Drug MMF n=8 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid MPA Raw	29 mcg*h/mL Standard Deviation 20.3
Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid MPAG Raw	487 mcg*h/mL Standard Deviation 185
Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid MPAG (MPA Equivalents)	289 mcg*h/mL Standard Deviation 109

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants > 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants < 24 months

Population: The PK population was used for the analysis.

The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was obtained directly from the measured plasma concentration-time curves.

Outcome measures

Outcome measures
Measure	Drug MMF n=8 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide MPA Raw	7.98 mcg/mL Standard Deviation 3.69
Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide MPAG Raw	54.6 mcg/mL Standard Deviation 26.8
Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide MPAG (MPA Equivalents)	32.4 mcg/mL Standard Deviation 15.9

SECONDARY outcome

Population: The PK population was used for the analysis.

Tmax is the amount of time after dosing to when the maximum concentration of MPA and MPAG was achieved.

Outcome measures

Outcome measures
Measure	Drug MMF n=8 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide MPA Raw	1.35 hour Interval 0.5 to 2.03
Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide MPAG Raw	1.99 hour Interval 1.52 to 4.13

SECONDARY outcome

Timeframe: Up to Day 32

Population: The safety population included all participants who were enrolled in the trial

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event.

Outcome measures

Outcome measures
Measure	Drug MMF n=9 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Number of Participants With Adverse Events and Serious Adverse Events Participants with AE	1 participants
Number of Participants With Adverse Events and Serious Adverse Events Participants with SAE	0 participants

SECONDARY outcome

Population: The PK population included all randomized and replaced participants adherent to the PK section of the protocol.

Mycophenolic Acid Glucuronide (MPAG) is an active metabolite of Mycophenolic Acid (MPA).

Outcome measures

Outcome measures
Measure	Drug MMF n=8 Participants Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 0.0	0.786 mcg/mL Standard Deviation 0.681
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 0.50	9.03 mcg/mL Standard Deviation 4.34
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 0.75	5.67 mcg/mL Standard Deviation 3.14
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 1.00	5.84 mcg/mL Standard Deviation 3.13
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 1.50	6.16 mcg/mL Standard Deviation 5.08
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 2.00	6.23 mcg/mL Standard Deviation 4.54
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 4.00	1.89 mcg/mL Standard Deviation 1.90
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 8.00	1.38 mcg/mL Standard Deviation 1.72
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPA at 12.00	0.676 mcg/mL Standard Deviation 0.795
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 0.00	26.2 mcg/mL Standard Deviation 20.4
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 0.50	26.5 mcg/mL Standard Deviation 1.13
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 0.75	45.8 mcg/mL Standard Deviation 28.2
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 1.00	37.2 mcg/mL Standard Deviation 4.81
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 1.50	43.2 mcg/mL Standard Deviation 12.9
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 2.00	51.0 mcg/mL Standard Deviation 27.9
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 4.00	46.3 mcg/mL Standard Deviation 21.3
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 8.00	19.2 mcg/mL Standard Deviation 13.4
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point Raw MPAG at 12.00	14.6 mcg/mL Standard Deviation 7.35

Adverse Events

Drug MMF

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Drug MMF n=9 participants at risk Participants receiving drug MMF twice daily along with stable concomitant doses of cyclosporine (for at least 2 full days) and corticosteroids as per center practice for at least 7 days prior to Pharmacokinetic (PK) sampling were observed up to Day 16
General disorders Pyrexia	11.1% 1/9 • Up to Day 32 All participants enrolled were included in the safety analysis.

Additional Information

F. Hoffmann-La Roche AG

Roche Trial Information Hotline

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER