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

NCT02630563 | Terminated Phase 2 Results

• 1 other identifier: PA16497
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Pediatric Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid

  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

  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

  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

  Up to Day 32

• Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point

  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

Study Arms (1)

Mycophenolate Mofetil+Corticosteroids+Cyclosporine

EXPERIMENTAL

Part 1: Participants will receive mycophenolate mofetil. Part 2: Participants will receive mycophenolate mofetil along with cyclosporine and corticosteroids.

Drug: Corticosteroids; Drug: Cyclosporine; Drug: mycophenolate mofetil

Interventions

Corticosteroids DRUG

Corticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice.

Mycophenolate Mofetil+Corticosteroids+Cyclosporine

Cyclosporine DRUG

Cyclosporine will be administered as per center practice.

Mycophenolate Mofetil+Corticosteroids+Cyclosporine

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.

Also known as: CellCept

Mycophenolate Mofetil+Corticosteroids+Cyclosporine

Eligibility Criteria

• Age: 3 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

Unknown Facility

San Francisco, California, 94143-0116, United States

Location

Unknown Facility

New York, New York, 10032-3784, United States

Location

MeSH Terms

Interventions

Adrenal Cortex Hormones; Cyclosporine; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Limitations and Caveats

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.

Results Point of Contact

• Title: F. Hoffmann-La Roche AG
• Organization: Roche Trial Information Hotline

global.trial_information@roche.com

+41 61 6878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2015
• First Posted: December 15, 2015
• Study Start: May 1, 2003
• Primary Completion: January 1, 2005
• Study Completion: January 1, 2005
• Last Updated: May 19, 2016
• Results First Posted: April 12, 2016

Record last verified: 2015-12

Locations

US (2)