Enteric-coated Mycophenolate Sodium (EC-MPS) and Mycophenolate Mofetil (MMF) in Renal Transplant Patients With Gastrointestinal (GI) Intolerance

NCT00400400 | Completed Phase 4 Results

• 1 other identifier: CERL080AUS51
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 53

Brief Summary

Treatment with the immunosuppressive drug mycophenolate mofetil (MMF) may result in gastrointestinal (GI) complications in some patients. This study will investigate the safety and tolerability of converting kidney transplant recipients with gastrointestinal symptoms from their current treatment of mycophenolate mofetil (MMF) to treatment with enteric-coated mycophenolate sodium (EC-MPS).

Conditions

Renal Transplantation

Keywords

RenalTransplantation; KidneyTransplantation; MPA; EC-MPS

Outcome Measures

Primary Outcomes (1)

• The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy

  Response assessed using the Gastrointestinal Symptom Rating Scale (GSRS), designed to assess common symptoms with gastrointestinal (GI) disorders. The GSRS has 5 subscales (reflux, diarrhea, constipation, abdominal pain and indigestion) producing a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). The total score is an average of scores across all 15 items; a higher score indicates more GI symptoms. Response was defined as Day 30 improvement in the GSRS Total Score (change from baseline) of greater than or equal to 0.3. Minimum score is 1; maximum score is 7.

  Baseline, Day 30

Secondary Outcomes (6)

• Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)

  30 days

• Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score

  Baseline, Day 30

• Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment

  30 days

• Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score

  Baseline, Day 30

• Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment

  Baseline to Day 30

Study Arms (2)

Enteric-coated mycophenolate sodium

EXPERIMENTAL

Enteric-coated mycophenolate sodium tablets taken orally twice a day (in the morning and in the evening) at a dose equimolar to the dose of mycophenolate mofetil the participant was taking prior to start of the study + Placebo to mycophenolate mofetil capsules taken orally twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Drug: Enteric-coated mycophenolate sodium (EC-MPS); Drug: Placebo to mycophenolate mofetil

Mycophenolate mofetil

ACTIVE COMPARATOR

Mycophenolate mofetil capsules taken orally twice a day (in the morning and in the evening) at the dose the participant was taking prior to study start + Placebo to mycophenolate sodium tablets taken twice a day for 30 days. Participants remained on their standard immunosuppressive regimen of calcineurin inhibitors (CNI) (Cyclosporin A or Tacrolimus) administered with or without corticosteroids throughout the study.

Drug: Mycophenolate mofetil; Drug: Placebo to mycophenolate sodium

Interventions

Enteric-coated mycophenolate sodium (EC-MPS) DRUG

Enteric-coated mycophenolate sodium supplied as 180 mg tablets.

Also known as: Myfortic®

Enteric-coated mycophenolate sodium

Mycophenolate mofetil DRUG

Mycophenolate mofetil supplied as 250 mg capsules.

Mycophenolate mofetil

Placebo to mycophenolate sodium DRUG

Placebo to mycophenolate sodium matching tablets.

Mycophenolate mofetil

Placebo to mycophenolate mofetil DRUG

Placebo to mycophenolate mofetil matching capsules.

Enteric-coated mycophenolate sodium

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 18-75 years, Recipients of first or second cadaveric, living unrelated or living related kidney transplant
• Recipients who are at least 4 weeks post renal transplantation with stable renal function, Patients currently receiving MMF (all dosages are allowed) and either cyclosporine USP (MODIFIED) or tacrolimus with or without corticosteroids as part of their immunosuppressive regimen for at least 2 weeks prior to study start
• Patients with at least one mild and/or moderate and/or severe upper or lower gastrointestinal (GI) complaints clearly associated with MMF therapy as determined by the treating physician. Additional mild GI complaints may coexist
• Patients' immunosuppressive regimen other than steroids (doses and type) as well as medication for treatment of GI symptoms must be unchanged for at least 1 week prior to study start
• Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

You may not qualify if:

• Multi-organ transplant patients (e.g. kidney and pancreas) or previous transplant with any other organ different from kidney (second kidney transplant is allowed)
• History of GI disorder (diarrhea, Gastroesophageal Reflux Disease (GERD), dyspepsia, Inflammatory Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) prior to transplantation
• Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MMF, Modification of GI medication or MMF dose within last 1 week
• Evidence of graft rejection, treatment of acute rejection, or unstable renal function within 4 weeks prior to the Baseline visit, Patients who have received an investigational immunosuppressive drug within 4 weeks prior to study entry
• Patients with a history of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin
• Pregnant or nursing (lactating) women, Women of child-bearing potential (WOCBP) not using an acceptable method of contraception such as: surgical sterilization, hormonal contraception, or double-barrier methods.
• Contraception should be maintained throughout the study and for 4 weeks after study drug discontinuation.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (53)

AKDHC Medical Research Services, LLC

Phoenix, Arizona, 85012, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

National Institute of Transplantation

Los Angeles, California, 90057, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Diego

San Diego, California, 92103-8401, United States

Location

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California

San Francisco, California, 94143, United States

Location

Denver Nephrology

Denver, Colorado, 80218, United States

Location

University of Colorado Health Science Center

Denver, Colorado, 80262, United States

Location

Yale University Transplantation

New Haven, Connecticut, 06520, United States

Location

Washington Hospital Transplant Research

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610-0224, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Clarian Health Partners

Indianapolis, Indiana, 46202, United States

Location

Univ of KS Medical Ctr

Kansas City, Kansas, 64111, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Northwest Louisiana Nephrology Research

Shreveport, Louisiana, 71101, United States

Location

WKHS/LSUHSC Regional Transplant Center

Shreveport, Louisiana, 71103, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Mid-Atlantic Nephrology Associates

Baltimore, Maryland, 21228, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

St. John Hospital Medical Center

Detroit, Michigan, 48236, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

St. Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

St. Baranabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UNC Chapel Hill

Chapel Hill, North Carolina, 27599-7211, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Wake Forest

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Pinnacle Health at Harrisburg Hospital

Harrisburg, Pennsylvania, 17105, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

The University of Tennessee Health Science Center

Memphis, Tennessee, 38104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2372, United States

Location

CRSTI

Dallas, Texas, 75230, United States

Location

Baylor All Saints

Fort Worth, Texas, 76104, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0533, United States

Location

University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 98195-6521, United States

Location

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 15, 2006
• First Posted: November 16, 2006
• Study Start: October 1, 2006
• Primary Completion: June 1, 2008
• Last Updated: August 15, 2011
• Results First Posted: August 15, 2011

Record last verified: 2011-07

Locations

US (53)