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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
400
Enteric-coated mycophenolate sodium supplied as 180 mg tablets.
Mycophenolate mofetil supplied as 250 mg capsules.
Placebo to mycophenolate sodium matching tablets.
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.
Time frame: Baseline, Day 30
Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)
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.
Time frame: 30 days
Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score
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.
Time frame: Baseline, Day 30
Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment
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).
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Placebo to mycophenolate mofetil matching capsules.
AKDHC Medical Research Services, LLC
Phoenix, Arizona, 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
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
University of California San Diego
San Diego, California, United States
University of California, San Diego
San Diego, California, United States
University of California
San Francisco, California, United States
Denver Nephrology
Denver, Colorado, United States
...and 43 more locations
Time frame: 30 days
Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score
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.
Time frame: Baseline, Day 30
Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment
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.
Time frame: Baseline to Day 30
Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores
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.
Time frame: Baseline, Day 30