A Study of CellCept (Mycophenolate Mofetil) in Combination Therapy in Liver Transplant Patients.

Roche

Status and phase: Completed; Phase 4

Conditions: Liver Transplantation

Treatments: Drug: Mycophenolate mofetil, Standard dose; Drug: Mycophenolate mofetil, adjusted dose; Drug: Corticosteroids, PO; Drug: Tacrolimus; Drug: Corticosteroids, IV

Study type: Interventional

Funder types: Industry

Identifiers

NCT00545402

ML21273

Details and patient eligibility

About

This 2 arm study will compare the efficacy and safety of two CellCept-containing treatment regimens in de novo liver transplant patients. Patients will be randomized into one of two groups, to receive either CellCept (at a starting dose of 3g/day po, adjusted according to exposure) standard dose tacrolimus and corticosteroids (10-15 mg/kg i.v. on day 0), or fixed dose CellCept 2g/day po, standard dose tacrolimus and corticosteroids (10-15mg/kg i.v. on day 0, then reducing from 20mg to 5mg over 6 months, and discontinuing after 6 months). The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult patients, >=18 years of age;
• recipient of a first orthotopic liver transplant.

Exclusion criteria

• history of organ transplants;
• patient receiving a multi-organ transplant;
• calculated creatinine clearance <=30mL/min before transplant;
• leukocyte count < 2000/mm3 at randomization;
• history of cancer within past 5 years, except for successfully treated basal cell or squamous cell cancer, or in situ cervical cancer;
• pregnant or breast-feeding females, or females of childbearing age not using effective contraception.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 2 patient groups

MMF, Adjusted Dose; Tacrolimus; Corticosteroids

Experimental group

Description:

Participants received mycophenolate mofetil (MMF) 3 grams per day (g/d), orally (PO), twice per day (BID) with meals from Day 0 to Day 4; the dose was adjusted based on total exposure (AUC) using the Bayesian method with limited sampling strategy on Days 5 and 14, Months 1, 13, 6, 9, and 12. Participants also received tacrolimus adjusted to a target trough level of 8 to (-) 12 nanograms per milliliter (ng/mL) from Day 0 to Month 1; the dose was adjusted to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 milligrams per kilogram (mg/kg), intravenously (IV), pre-operation on Day 0.

Treatment:

Drug: Corticosteroids, IV

Drug: Tacrolimus

Drug: Mycophenolate mofetil, adjusted dose

MMF, Standard Dose; Tacrolimus; Corticosteroids

Active Comparator group

Description:

Participants received MMF 2 g/d, PO, BID with meals from Day 0 to Month 12. Participants also received tacrolimus adjusted to a target trough level of 8-12 ng/mL from Day 0 to Month 1; the dose was reduced to reach a target trough level of 3-8 ng/mL from the end of Month 1 through Month 12. Participants also received corticosteroids 10-15 mg/kg, IV, pre-operation on Day 0; followed by 20 mg/d, PO, 4 times per day (QDS) from Day 0 through Month 1; 15 mg/d, PO, 3 times per day (TID) from the end of Month 1 through Month 2; 10 mg/d, PO, BID from the end of Month 2 through Month 3; and 5 mg/d once per day from the end of Month 3 through Month 6.

Treatment:

Drug: Corticosteroids, IV

Drug: Tacrolimus

Drug: Corticosteroids, PO

Drug: Mycophenolate mofetil, Standard dose