Clinical Trial Result Information
Protocol number
PA16497
Title of Study
A study of the safety, tolerability and pharmacokinetics of oral CellCept (mycophenolate mofetil, MMF) in pediatric liver transplant recipients on concomitant treatment with Cyclosporine and Corticosteroids.
Sponsor
Roche Global Development
Company division
Pharmaceutical
Product name
CellCept
Generic name
mycophenolate mofetil
Therapeutic area
Liver transplantation
Clinical study summary
Part I was an open-label, multi-center, non-controlled study. Part II was to be an open-label, multi-center, single-arm study, but the study was terminated before the start of Part II.
Study center(s)
2 centers in USA.
Phase of development
IV
Objectives
The objective of part I of the study was to estimate the dose predicted to achieve an exposure of 58 μg.h/mL in stable pediatric hepatic transplant patients. This estimated dose was to be used in the second, confirmatory part of the study.
The objective of part II of the study was to assess the pharmacokinetics and safety of oral MMF in the immediate and late post-transplant periods in pediatric liver transplant patients.
The study was terminated after Part I, due to recruitment difficulties, and Part II was not conducted.
Methodology
Patients who were at least 6 months post liver transplant were eligible for the study. After a screening period of between -14 and -1 days, patients were scheduled to have a single 12 hour pharmacokinetic profile taken on study day 1. Patients were receiving CellCept at stable doses per center practice for at least 7 days prior to PK sampling.
On day 1, a 12 hour PK profile was collected for each patient. Blood samples were collected at pre-dose and at intervals up to 12≥ hours post-dose. Adverse events were recorded throughout the study, laboratory safety assessments and vital signs were performed at baseline.
Number of patients (planned/analyzed)
9 patients (planned to enroll 12 patients).
Diagnosis and main criteria for inclusion
Pediatric transplant recipients aged 9 months to 12 years of age inclusive, who had received a first liver allograft from a cadaveric or living donor.
Test product, dose and mode of administration or test procedure
CellCept (mycophenolate mofetil) 200-424 mg/m2 b.i.d.
Duration of treatment
≥ 7 days
Reference therapy, dose and mode of administration or reference procedure
Not applicable
Criteria for evaluation (efficacy, safety)
Pharmacokinetics: AUC0-12h, Cmax, Tmax, Safety: Adverse events.
Statistical methods
All pharmacokinetic parameters were summarized descriptively by age group and by visit. The summary statistics included arithmetic means, geometric means, ranges, standard deviation and coefficients of variation.
Summary (efficacy, safety, other results)
Pharmacokinetics: In this study, patients’ CellCept doses of 200 - 424 mg/m2 bid. gave AUCs of mycophenolic acid of less than 58 μg.h/mL in 7 out of 8 cases. Only one patient, who achieved an AUC of greater than 58 μg.h/mL, was considered an outlier because the AUC was more than 2-fold higher than the other patients.
Based on the following assumptions:
1) that mycophenolic acid exhibits linear PK,
2) that an AUC achieved ≥ 6 months post-transplant is two-fold higher than an AUC in the immediate post-transplant period,
3) an AUC of 29 μg.h/mL provides effective immunosuppression in the immediate post-transplant period,
the study demonstrated that a dose of 740-806mg/m2 would be required in the early post-transplant period to achieve adequate immunosuppression if the same dose of CellCept is continued from transplant until 6 months post-transplant.
Safety: One subject reported one adverse event (pyrexia) during the course of the study. This adverse event was mild in intensity and was assessed by the investigator as unrelated to trial treatment. There were no serious adverse events, no deaths or adverse events that led to the withdrawal of a patient recorded during the study.
Conclusions
An AUC of 58 μg.h/mL at 6 months post-transplant is the expected AUC in adults receiving the dose of CellCept that was associated with a reduction in acute rejection. In this study, patients received CellCept doses of 200-424 mg/m2 bid at 6 months post-transplant and in 7 out of 8 cases these patients had AUCs < 58 μg.h/mL at 6 months post-transplant. A dose of 740-806 mg/m2 would be required in the early post-transplant period to achieve adequate immunosuppression at 6 months post-transplant.
Date of report
12/1/2005
Click here for the protocol registry listing of this trial.
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