Renal Transplantation
Conditions
Keywords
RenalTransplantation, KidneyTransplantation, MPA, EC-MPS
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).
Interventions
DRUGEnteric-coated mycophenolate sodium (EC-MPS)
Enteric-coated mycophenolate sodium supplied as 180 mg tablets.
DRUGMycophenolate mofetil
Mycophenolate mofetil supplied as 250 mg capsules.
DRUGPlacebo to mycophenolate sodium
Placebo to mycophenolate sodium matching tablets.
Placebo to mycophenolate mofetil matching capsules.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 * Females of childbearing potential must have a negative pregnancy test prior to the inclusion period. The test should be performed locally at Baseline visit. If positive, the patient will not be included. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication * Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.
Exclusion criteria
* 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. Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | 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 | 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). |
| 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 in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | 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 | 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. |
| Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 199 |
| 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. | 197 |
| Total | 396 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Problem | 1 | 0 |
| Overall Study | Adverse Event | 9 | 8 |
| Overall Study | Did not receive study drug | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Enteric-coated Mycophenolate Sodium | Mycophenolate Mofetil | Total |
|---|---|---|---|
| Age Continuous | 48.4 Years STANDARD_DEVIATION 13.4 | 48.4 Years STANDARD_DEVIATION 12.6 | 48.4 Years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 105 Participants | 95 Participants | 200 Participants |
| Sex: Female, Male Male | 94 Participants | 102 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 199 | 89 / 197 |
| serious Total, serious adverse events | 7 / 199 | 11 / 197 |
Outcome results
Primary
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
Population: Intention-to-treat (ITT) population consisted of all randomized participants who received at least one dose of study drug. 2 participants in the enteric-coated mycophenolate sodium group were excluded from the analysis because they had no baseline data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy | Response | 123 Participants |
| Enteric-coated Mycophenolate Sodium | The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy | No Response | 74 Participants |
| Mycophenolate Mofetil | The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy | Response | 109 Participants |
| Mycophenolate Mofetil | The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy | No Response | 88 Participants |
Secondary
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
Population: Participants from the Intention-to-treat (ITT) population consisting of all randomized participants who received at least one dose of study drug for whom data was available for analysis. n in each of the categories is the number of participants with data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score: BL ( n= 197,197) | 94.3 Score on a scale | Standard Deviation 17.9 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score : Day 30 (n= 195,192) | 105.0 Score on a scale | Standard Deviation 18.4 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score : Change from BL (n=193,192) | 10.7 Score on a scale | Standard Deviation 16.4 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: BL (n= 197, 197) | 46.7 Score on a scale | Standard Deviation 10.6 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: Day 30 (n= 195, 192) | 52.6 Score on a scale | Standard Deviation 10.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: Change from BL (n= 193, 192) | 5.9 Score on a scale | Standard Deviation 9.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: BL (n= 196, 197) | 11.9 Score on a scale | Standard Deviation 2.7 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: Day 30 (n= 195, 192) | 13.2 Score on a scale | Standard Deviation 2.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: Change from BL (n= 192, 192) | 1.3 Score on a scale | Standard Deviation 2.9 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: BL (n= 196, 197) | 21.7 Score on a scale | Standard Deviation 3.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: Day 30 (n= 195, 192) | 23.7 Score on a scale | Standard Deviation 3.4 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: Change from BL (n= 192, 192) | 2.1 Score on a scale | Standard Deviation 3.2 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: BL (n= 197, 197) | 10.7 Score on a scale | Standard Deviation 2.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: Day 30 (n= 195, 192) | 11.9 Score on a scale | Standard Deviation 3 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: Change from BL (n= 193, 192) | 1.2 Score on a scale | Standard Deviation 2.6 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: BL (n= 197, 197) | 3.3 Score on a scale | Standard Deviation 1 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: Day 30 (n= 194, 192) | 3.6 Score on a scale | Standard Deviation 0.8 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: Change from BL (n= 192, 192) | 0.2 Score on a scale | Standard Deviation 1 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: Day 30 (n= 195, 192) | 11.6 Score on a scale | Standard Deviation 2.8 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score: BL ( n= 197,197) | 93.4 Score on a scale | Standard Deviation 18 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: BL (n= 196, 197) | 21.5 Score on a scale | Standard Deviation 3.9 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score : Day 30 (n= 195,192) | 103.5 Score on a scale | Standard Deviation 18.1 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: Change from BL (n= 192, 192) | 0.3 Score on a scale | Standard Deviation 0.9 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Overall Total Score : Change from BL (n=193,192) | 10.2 Score on a scale | Standard Deviation 17.5 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: Day 30 (n= 195, 192) | 23.3 Score on a scale | Standard Deviation 3.8 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: BL (n= 197, 197) | 46.6 Score on a scale | Standard Deviation 10.3 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: Change from BL (n= 193, 192) | 1.2 Score on a scale | Standard Deviation 2.7 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: Day 30 (n= 195, 192) | 51.9 Score on a scale | Standard Deviation 10.7 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Physical Function: Change from BL (n= 192, 192) | 1.9 Score on a scale | Standard Deviation 4 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | GI Symptom: Change from BL (n= 193, 192) | 5.4 Score on a scale | Standard Deviation 10.2 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: Day 30 (n= 194, 192) | 3.6 Score on a scale | Standard Deviation 0.7 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: BL (n= 196, 197) | 11.6 Score on a scale | Standard Deviation 2.9 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Social Function: BL (n= 197, 197) | 10.4 Score on a scale | Standard Deviation 2.8 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: Day 30 (n= 195, 192) | 13.1 Score on a scale | Standard Deviation 2.6 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Medical treatment: BL (n= 197, 197) | 3.4 Score on a scale | Standard Deviation 1 |
| Mycophenolate Mofetil | Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores | Emotional Status: Change from BL (n= 192, 192) | 1.5 Score on a scale | Standard Deviation 3 |
Secondary
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
Population: Intention-to-treat (ITT) population consisted of all randomized participants who received at least one dose of study drug. 2 participants in the enteric-coated mycophenolate sodium group were excluded from the analysis because they had no baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score | -0.6 change in score on a scale | Standard Deviation 0.9 |
| Mycophenolate Mofetil | Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score | -0.5 change in score on a scale | Standard Deviation 1 |
Secondary
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
Population: Intention to treat (ITT) population consisted of all randomized participants who received at least one dose of study drug. n in each of the categories is the number of participants with data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Baseline (n= 198,195) | 0.7 Score on a scale | Standard Deviation 0.4 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Day 30 (n=193, 191) | 0.4 Score on a scale | Standard Deviation 0.4 |
| Enteric-coated Mycophenolate Sodium | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Change from Baseline to Day 30 (n=193,189) | -0.3 Score on a scale | Standard Deviation 0.4 |
| Mycophenolate Mofetil | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Baseline (n= 198,195) | 0.6 Score on a scale | Standard Deviation 0.4 |
| Mycophenolate Mofetil | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Day 30 (n=193, 191) | 0.4 Score on a scale | Standard Deviation 0.4 |
| Mycophenolate Mofetil | Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score | Change from Baseline to Day 30 (n=193,189) | -0.2 Score on a scale | Standard Deviation 0.4 |
Secondary
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
Population: Intention-to-treat (ITT) population consisted of all randomized participants who received at least one dose of study drug. 2 participants in the enteric-coated mycophenolate sodium group were excluded from the analysis because they had no baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion: Day 30 | 2.1 Score on a scale | Standard Deviation 1 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Change from BL to Day 30 | -0.4 Score on a scale | Standard Deviation 1.1 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Day 30 | 2.4 Score on a scale | Standard Deviation 1.6 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Baseline | 2.3 Score on a scale | Standard Deviation 1.1 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion: Change from BL to Day 30 | -0.7 Score on a scale | Standard Deviation 1.2 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Day 30 | 1.8 Score on a scale | Standard Deviation 0.9 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion : Baseline | 2.8 Score on a scale | Standard Deviation 1.3 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Change from BL to Day 30 | -0.5 Score on a scale | Standard Deviation 1.1 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Baseline | 2.2 Score on a scale | Standard Deviation 1.2 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Baseline | 2.2 Score on a scale | Standard Deviation 1.3 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Change from BL to Day 30 | -0.9 Score on a scale | Standard Deviation 1.7 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Day 30 | 1.7 Score on a scale | Standard Deviation 1.1 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Day 30 | 1.7 Score on a scale | Standard Deviation 0.9 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Change from BL o Day 30 | -0.5 Score on a scale | Standard Deviation 1.3 |
| Enteric-coated Mycophenolate Sodium | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Baseline (BL) | 3.3 Score on a scale | Standard Deviation 1.7 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Change from BL o Day 30 | -0.5 Score on a scale | Standard Deviation 1.5 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Baseline (BL) | 3.3 Score on a scale | Standard Deviation 1.7 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Day 30 | 2.5 Score on a scale | Standard Deviation 1.6 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Diarrhea: Change from BL to Day 30 | -0.8 Score on a scale | Standard Deviation 1.6 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion : Baseline | 2.8 Score on a scale | Standard Deviation 1.3 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion: Day 30 | 2.4 Score on a scale | Standard Deviation 1.2 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Indigestion: Change from BL to Day 30 | -0.5 Score on a scale | Standard Deviation 1.4 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Baseline | 2.1 Score on a scale | Standard Deviation 1.1 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Day 30 | 1.8 Score on a scale | Standard Deviation 0.9 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Constipation: Change from BL to Day 30 | -0.3 Score on a scale | Standard Deviation 1 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Baseline | 2.5 Score on a scale | Standard Deviation 1.1 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Day 30 | 2.0 Score on a scale | Standard Deviation 1.1 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Abdominal pain: Change from BL to Day 30 | -0.5 Score on a scale | Standard Deviation 1.2 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Baseline | 2.2 Score on a scale | Standard Deviation 1.4 |
| Mycophenolate Mofetil | Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment | Reflux : Day 30 | 1.7 Score on a scale | Standard Deviation 1.1 |
Secondary
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
Population: Intent-to-treat population consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR) | BPAR | 0 Participants |
| Enteric-coated Mycophenolate Sodium | Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR) | TAR | 0 Participants |
| Mycophenolate Mofetil | Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR) | BPAR | 1 Participants |
| Mycophenolate Mofetil | Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR) | TAR | 1 Participants |
Secondary
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).
Time frame: 30 days
Population: Intention to treat (ITT) population consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enteric-coated Mycophenolate Sodium | Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment | Study drug change or interruption: YES | 11 Participants |
| Enteric-coated Mycophenolate Sodium | Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment | Study drug change or interruption: NO | 188 Participants |
| Mycophenolate Mofetil | Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment | Study drug change or interruption: YES | 12 Participants |
| Mycophenolate Mofetil | Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment | Study drug change or interruption: NO | 185 Participants |