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Due to extremely slow recruitment, infrequent use of combination triple therapy (MMF, cyclosporine, steroids), study was discontinued; Part 2 was not conducted.
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The study is planned to be conducted in 2 parts. The first part (open label, multi-center, non-controlled) of the study will estimate a dose that would provide a mycophenolic acid (MPA) exposure in pediatric participant that is comparable to that achieved in adult liver transplant participants receiving the approved dose of mycophenolate mofetil (MMF, CellCept). The second part (open-label, multi-center, single-arm Phase IV study) of the study will provide the pharmacokinetics, efficacy and safety profile of the proposed dose in the immediate post-transplant period. This study will be conducted at two centers based in the United States of America. Twelve pediatric transplant participants receiving a first liver allograft from a cadaveric or living donor will be enrolled in this study. Stable pediatric liver transplant participants who are at least 6 months post-transplant and who were already receiving stable dose of MMF in combination with cyclosporine will be enrolled into the study. Participants should have received stable MMF dose according to center practice for at least seven days in order to get steady state pharmacokinetics (PK). Participants also should have received stable concomitant doses of cyclosporine (for at least 2 days) and corticosteroids per center practice. Participants will be aged between 9 months and 12 years, with at least 6 participants greater than or equal to (>/=) 9 months and less than (<) 36 months, of whom at least 2 will be <24 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mycophenolate Mofetil+Corticosteroids+Cyclosporine | Experimental | Part 1: Participants will receive mycophenolate mofetil. Part 2: Participants will receive mycophenolate mofetil along with cyclosporine and corticosteroids. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Corticosteroids | Drug | Corticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area | 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). | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco | California | 94143-0116 | United States | |||
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Cyclosporine | Drug | Cyclosporine will be administered as per center practice. |
|
| mycophenolate mofetil | Drug | Part 1: Mycophenolate mofetil will be administered as per center practice. Part 2: Mycophenolate mofetil will be administered as per dose determined in Part 1. |
|
|
| 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 |
| Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide | The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was obtained directly from the measured plasma concentration-time curves. | 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 |
| Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide | Tmax is the amount of time after dosing to when the maximum concentration of MPA and MPAG was achieved. | 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 |
| Number of Participants With Adverse Events and Serious Adverse Events | 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. | Up to Day 32 |
| Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point | Mycophenolic Acid Glucuronide (MPAG) is an active metabolite of Mycophenolic Acid (MPA). | 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 |
| New York |
| New York |
| 10032-3784 |
| United States |
| COMPLETED |
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| NOT COMPLETED |
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|
All Patient Population included all participants who were enrolled in the trial
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid | 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). | The PK population included all randomized and replaced participants adherent to the PK section of the protocol | Posted | Mean | Standard Deviation | mcg*h/mL | 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 |
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| |||||||||||||||||||||||||||||||||||
| Secondary | Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide | The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was obtained directly from the measured plasma concentration-time curves. | The PK population was used for the analysis. | Posted | Mean | Standard Deviation | mcg/mL | 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 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide | Tmax is the amount of time after dosing to when the maximum concentration of MPA and MPAG was achieved. | The PK population was used for the analysis. | Posted | Median | Full Range | hour | 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 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events and Serious Adverse Events | 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. | The safety population included all participants who were enrolled in the trial | Posted | Number | participants | Up to Day 32 |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area | 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). | The pharmacokinetic (PK) population included all randomized and replaced participants adherent to the PK section of the protocol. | Posted | Mean | Standard Deviation | mcg*h/mL | 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 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point | Mycophenolic Acid Glucuronide (MPAG) is an active metabolite of Mycophenolic Acid (MPA). | The PK population included all randomized and replaced participants adherent to the PK section of the protocol. | Posted | Mean | Standard Deviation | mcg/mL | 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 |
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|
Up to Day 32
All participants enrolled were included in the safety analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 9 | 1 | 9 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA (8.0) | Systematic Assessment |
|
Part I of the study was terminated early with 9 participants enrolled (8 of which were evaluable for PK), and Part II of the study was not performed due to extremely slow recruitment and the infrequent use of the combination of triple therapy.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| F. Hoffmann-La Roche AG | Roche Trial Information Hotline | +41 61 6878333 | global.trial_information@roche.com |
| ID | Term |
|---|---|
| D000305 | Adrenal Cortex Hormones |
| D016572 | Cyclosporine |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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