Gastrointestinal Tolerability of MMF vs EC-MPS in Maintenance Transplant Patients Treated With Calcineurin Inhibitors (MOTOR-MPA)

A Single Centre, Prospective, Open-Label, Parallel Group, Randomized Study to Compare the Gastrointestinal Tolerability of Mycophenolate Mofetil (MMF, CellCept) and Enteric-Coated Mycophenolate Sodium (EC-MPS, Myfortic) in Maintenance Transplant Patients Treated With Calcineurin Inhibitors

The purpose of the study is to assess the gastrointestinal tolerability of EC-MPS compared to MMF in maintenance transplant patients on a calcineurin inhibitor regimen, who require MMF dose reductions of 25% or more due to GI complications. The tested hypothesis is that the EC-MPS treatment is superior to the MMF therapy in terms of tolerability and that patients on the EC-MPS formulation will be able to tolerate higher doses compared to those on MMF.

Study Overview

• Status: Unknown
• Conditions: Organ Transplantation
• Intervention / Treatment: Drug: MMF; Drug: EC-MPS

Detailed Description

The use of mycophenolate mofetil (MMF) in combination with a calcineurin inhibitor (CNI: tacrolimus or cyclosporine) has been shown to improve graft survival in renal, cardiac and liver transplantation patients. However, its use has been associated with significant side effects, including gastrointestinal complications, causing dose reductions, interruption or termination of the therapy. An alternate formulation: enteric coated mycophenolate sodium (EC-MPS) was designed to alleviate the severity of upper gastrointestinal side effects. Several trials detailed in the protocol suggest a benefit in GI related health following conversion from MMF to EC-MPS, however we believe that robust data are lacking.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • Toronto General Hospital - Multi Organ Transplant Program
      • Contact: Jill Sheedy, RN BScN; Phone Number: 4540 416 340 4800; Email: jill.sheedy@uhn.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• recipients of liver or kidney or heart or lung or kidney/pancreas transplants
• at least 1 month post solid organ transplant
• on an immunosuppressive regimen which includes MMF in combination with cyclosporine A or tacrolimus
• previous MMF dose reduction of minimum of 25% of total dose due to at least one gastrointestinal complication with MMF therapy
• age of 18-75 years

Exclusion Criteria:

• less than 1 month post transplant
• allergy (hypersensitivity) to MPA, MMF, EC-MPS or to any ingredients of Myfortic or CellCept
• unwillingness or inability to give written consent
• pregnant or nursing women, or women planning to become pregnant
• patients with GI symptoms due to reasons other than related to MMF therapy
• active Post Transplant Lymphoproliferative Disease (PTLD)
• significant or uncontrolled concomitant infections or other serious medical problems
• active bacterial, viral or fungal infection
• inability to self-administer the Quality of Life questionnaires

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; MMF	Drug: MMF; Gradual optimization of drug dosage, as clinically tolerated.; Other Names: CellCept
Active Comparator: B; EC-MPS	Drug: EC-MPS; Conversion from MMF to EC-MPS. Gradual optimization of drug dosage, as clinically tolerated.; Other Names: Myfortic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of patients with at least 1 GI symptom that is continuing or starting after the 1-month dose stabilization period	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Analysis and comparison of various Gastrointestinal Symptom Rating and Quality of Life Questionnaire (the GSRS, GIQLI, PGWB,OTE for HRQoL) scores across and within the 2 cohorts.	At months 1, 3, 6, 12 post-study start
Incidence and severity of adverse events	months 3, 6, 12
Patient survival, graft survival and rejection episodes across the 2 cohorts	months 3, 6, 12
Dose reductions, interruptions, fractionations and patient withdrawals across the two cohorts due to adverse events	Months 6, 12

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: George Therapondos, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: January 29, 2008
• First Submitted That Met QC Criteria: January 29, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Estimate): February 17, 2009
• Last Update Submitted That Met QC Criteria: February 16, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: Quality of Life; Drug tolerance
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: 07-0398-A