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

Pediatric Liver Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02630563
• Other study ID #: PA16497
• Status: Terminated
• Phase: Phase 4
• First received: December 11, 2015
• Last updated: December 14, 2015
• Start date: May 2003
• Est. completion date: January 2005

Study information

• Verified date: December 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: January 2005
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 12 Years

Eligibility

Inclusion Criteria:

• Male or female participant must be between 3 months and 12 years of age

• Participant is a recipient of a first liver allograft from cadaveric or living donors

• Participant is a single-organ recipient (liver only)

• Female participants of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli International Units per milliliter (mIU/mL) within one week prior to PK sampling

• Female participants of childbearing potential must use two reliable forms of contraception simultaneously unless abstinence is the chosen method

• Effective contraception must be used before beginning of PK sampling

• Participants must be able to receive oral medication

• Participants must be at least 6 months post-transplant and had started on MMF in the early post-transplant period (within 2 weeks of transplant)

• Participants must be receiving stable doses of MMF per center practice for at least 7 days prior to PK sampling

• In addition, participants must be receiving stable doses of cyclosporine and corticosteroids, according to center practice

• Participant's parent/guardian are capable of understanding the purposes and risks of the study and must sign an informed consent for the study

Exclusion Criteria:

• Pregnant or nursing adolescents

• Participants who had undergone dialysis within two weeks before PK sampling

• Participants with active systemic infections

• Participants with absolute neutrophil counts (ANC) of less than 1300 per microliter (µL), or platelets counts less than 50 000/µL or hemoglobin at a concentration below a set lower limit (according to center practice, but not less than 8 grams per deciliter) at the time of study entry

• Participants with active peptic ulcer disease

• Participants with severe diarrhea (more than 5 watery stools per day) or other gastrointestinal disorders which might interfere with their ability to absorb oral medication

• History of positive human immunodeficiency virus (HIV) test

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pediatric Liver Transplantation

Intervention

Drug:
• Corticosteroids
Corticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice.
• Cyclosporine
Cyclosporine will be administered as per center practice.
• mycophenolate mofetil
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Normalized Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours (AUC0-12) of MPA		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No
Primary	Body Surface Area Normalized AUC0-12 of MPA		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No
Secondary	Plasma Concentration of MPA and its Metabolite Mycophenolic Acid Glucuronide (MPAG) at Each Time Point		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of MPA and MPAG		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No
Secondary	Time of Maximum Observed Plasma Concentration (Tmax) of MPA and MPAG		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No
Secondary	AUC0-12 of MPA and MPAG		Pre-dose (Hour 0), 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose on Day 1	No