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

Registration Number
NCT00400400
Lead Sponsor
Novartis Pharmaceuticals
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
400
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Enteric-coated mycophenolate sodiumEnteric-coated mycophenolate sodium (EC-MPS)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.
Enteric-coated mycophenolate sodiumPlacebo to mycophenolate mofetilEnteric-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.
Mycophenolate mofetilPlacebo to mycophenolate sodiumMycophenolate 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.
Mycophenolate mofetilMycophenolate mofetilMycophenolate 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.
Primary Outcome Measures
NameTimeMethod
The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) TherapyBaseline, Day 30

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale ScoreBaseline, Day 30

This is reflected by the total score. The total score incorporates lower and upper GI elements. GSRS overall score is the mean of 15 individual GI symptom scores, each rated on a 7- point scale: 1 = no discomfort, 2= minor discomfort, 3 = mild discomfort, 4 = moderate discomfort, 5 = moderately sever discomfort, 6 = severe discomfort and 7 = very severe discomfort. Change from Baseline was calculated using ANCOVA, model includes GSRS, center and treatment group.

Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)30 days

TAR was defined as an episode of acute rejection that was suspected on clinical grounds and was treated and confirmed by the investigator according to the patient's response to therapy.

BPAR was defined a treated acute rejection that was confirmed by biopsy. A graft core biopsy was performed before or within 24 hours of initiation of anti-rejection therapy and was assessed by the pathologist at the center according to the BANFF 1997 criteria.

Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total ScoreBaseline, Day 30

The Severity Score for each GI symptom for each participant was calculated based on the physician's evaluation of current GI symptoms recorded at Baseline and Day 30. For each of the 16 individual GI symptoms the severity score ranged from 0 (absent) to 3 (severe). The Overall Total Score is the Mean of severity ratings of the 16 individual symptoms.

Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment30 days

The number of participants with reported dose changes or interruption of study medication during the 30 days of treatment.The most common dose adjustments were dose increases back to baseline levels following a decrease or interruption and decreases due to abnormal laboratory value Adverse Events (leucopenia, thrombocytopenia, neutropenia, or anemia).

Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of TreatmentBaseline to Day 30

The GSRS has five subscales (reflux, diarrhea, constipation, abdominal pain, indigestion) producing a mean subscale score ranging from 1 (=no discomfort at all) to 7 (very severe discomfort). The mean score at baseline (BL), the mean score at Day 30 and the mean Change from BL to Day 30 is presented for each of the five subscales.

Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale ScoresBaseline, Day 30

The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI has 5 different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) that are rated on a 5-point scale from 0 to 4. The individual scores are summed to produce a total score of the 36 items for a total possible score of 0 to 144. Lower scores represent greater dysfunction.

Trial Locations

Locations (53)

The Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

National Institute of Transplantation

🇺🇸

Los Angeles, California, United States

Medical College of Georgia

🇺🇸

Augusta, Georgia, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

Northwest Louisiana Nephrology Research

🇺🇸

Shreveport, Louisiana, United States

Washington University School of Medicine

🇺🇸

St. Louis, Missouri, United States

East Carolina University

🇺🇸

Greenville, North Carolina, United States

Thomas Jefferson University Hospital

🇺🇸

Philadelphia, Pennsylvania, United States

University of Texas Medical Branch

🇺🇸

Galveston, Texas, United States

University of Florida College of Medicine

🇺🇸

Gainesville, Florida, United States

WKHS/LSUHSC Regional Transplant Center

🇺🇸

Shreveport, Louisiana, United States

University of Maryland

🇺🇸

Baltimore, Maryland, United States

St. Baranabas Medical Center

🇺🇸

Livingston, New Jersey, United States

Pinnacle Health at Harrisburg Hospital

🇺🇸

Harrisburg, Pennsylvania, United States

Mid-Atlantic Nephrology Associates

🇺🇸

Baltimore, Maryland, United States

CRSTI

🇺🇸

Dallas, Texas, United States

Baylor All Saints

🇺🇸

Fort Worth, Texas, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

University Hospitals of Cleveland

🇺🇸

Cleveland, Ohio, United States

Clarian Health Partners

🇺🇸

Indianapolis, Indiana, United States

University of California, San Diego

🇺🇸

San Diego, California, United States

Univ of KS Medical Ctr

🇺🇸

Kansas City, Kansas, United States

University of Washington

🇺🇸

Seattle, Washington, United States

David Geffen School of Medicine at UCLA

🇺🇸

Los Angeles, California, United States

Washington Hospital Transplant Research

🇺🇸

Washington, District of Columbia, United States

Piedmont Hospital

🇺🇸

Atlanta, Georgia, United States

University of Kentucky Medical Center

🇺🇸

Lexington, Kentucky, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

The University of Tennessee Health Science Center

🇺🇸

Memphis, Tennessee, United States

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

AKDHC Medical Research Services, LLC

🇺🇸

Phoenix, Arizona, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

University of California

🇺🇸

San Francisco, California, United States

Denver Nephrology

🇺🇸

Denver, Colorado, United States

University of Colorado Health Science Center

🇺🇸

Denver, Colorado, United States

Wake Forest

🇺🇸

Winston-Salem, North Carolina, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

St. John Hospital Medical Center

🇺🇸

Detroit, Michigan, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

University of Utah Hospitals and Clinics

🇺🇸

Salt Lake City, Utah, United States

Yale University Transplantation

🇺🇸

New Haven, Connecticut, United States

University of California San Diego

🇺🇸

San Diego, California, United States

St. Luke's Hospital of Kansas City

🇺🇸

Kansas City, Missouri, United States

UNC Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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