Enteric-coated Mycophenolate Sodium (EC-MPS) and Mycophenolate Mofetil (MMF) in Renal Transplant Patients With Gastrointestinal (GI) Intolerance
|Renal Transplantation||Drug: Enteric-coated mycophenolate sodium (EC-MPS) Drug: Mycophenolate mofetil Drug: Placebo to mycophenolate sodium Drug: Placebo to mycophenolate mofetil||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A 4-week, Multicenter, Double-blind, Double-dummy, Randomized, Parallel Group Study to Compare the Gastrointestinal Safety and Tolerability of EC-MPS & MMF When Administered in Combination With Calcineurin Inhibitors in Renal Transplant Recipients Experiencing Gastrointestinal Intolerance|
- The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy [ Time Frame: Baseline, 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.
- Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR) [ Time Frame: 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 Score [ Time Frame: Baseline, 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 Treatment [ Time Frame: 30 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 From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score [ Time Frame: Baseline, 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.
- Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment [ Time Frame: Baseline 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 Scores [ Time Frame: Baseline, 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.
|Study Start Date:||October 2006|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Experimental: Enteric-coated mycophenolate sodium
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)
Enteric-coated mycophenolate sodium supplied as 180 mg tablets.
Other Name: Myfortic®Drug: Placebo to mycophenolate mofetil
Placebo to mycophenolate mofetil matching capsules.
Active Comparator: Mycophenolate mofetil
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
Mycophenolate mofetil supplied as 250 mg capsules.Drug: Placebo to mycophenolate sodium
Placebo to mycophenolate sodium matching tablets.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00400400
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