Trial Outcomes & Findings for Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study. (NCT NCT01056822)
NCT ID: NCT01056822
Last Updated: 2014-12-03
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
89 participants
Primary outcome timeframe
at 12 months from baseline
Results posted on
2014-12-03
Participant Flow
Participant milestones
| Measure |
Mycophenolate Sodium (MPS)
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
42
|
|
Overall Study
Intention-to-treat (ITT) Population: YES
|
43
|
38
|
|
Overall Study
Intention-to-treat (ITT) Population: NO
|
4
|
4
|
|
Overall Study
Per-protocol (PP) Population: YES
|
29
|
25
|
|
Overall Study
Per-protocol (PP) Population: NO
|
18
|
17
|
|
Overall Study
Safety (SAF) Population: YES
|
46
|
40
|
|
Overall Study
Safety (SAF) Population: NO
|
1
|
2
|
|
Overall Study
COMPLETED
|
39
|
35
|
|
Overall Study
NOT COMPLETED
|
8
|
7
|
Reasons for withdrawal
| Measure |
Mycophenolate Sodium (MPS)
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Protocol Violation
|
6
|
5
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Multicenter, Randomized, Open-label Study to Assess Whether Treatment With Mycophenolate Sodium (MPS) Allows Higher Dose Optimization Versus Mycophenolate Mofetil (MMF) Leading to a Dose Reduction of Tacrolimus. Maximiza Study.
Baseline characteristics by cohort
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.88 years
STANDARD_DEVIATION 9.99 • n=5 Participants
|
48.50 years
STANDARD_DEVIATION 12.86 • n=7 Participants
|
50.83 years
STANDARD_DEVIATION 11.56 • n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
39 participants
n=5 Participants
|
36 participants
n=7 Participants
|
75 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus).
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Number of Participants Achieving at Least Two Mycophenolic Acid (MPA) Dose Steps Higher and Reducing Tacrolimus Dose at the End of the Study
# of participants with ≥2 MPA dose steps higher
|
0 number of participants
|
0 number of participants
|
|
Number of Participants Achieving at Least Two Mycophenolic Acid (MPA) Dose Steps Higher and Reducing Tacrolimus Dose at the End of the Study
# of participants with <2 MPA dose steps higher
|
43 number of participants
|
38 number of participants
|
PRIMARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus).
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Number of Participants That Achieved One Dose Step Higher With Mycophenolic Acid (MPA) or Mycophenolate Mofetil (MMF), According to the Treatment Group Assigned at the End of the Study (Final Visit) Compared to Baseline Dose
# of participants with < 1 MPA dose steps higher
|
6 study participants
|
8 study participants
|
|
Number of Participants That Achieved One Dose Step Higher With Mycophenolic Acid (MPA) or Mycophenolate Mofetil (MMF), According to the Treatment Group Assigned at the End of the Study (Final Visit) Compared to Baseline Dose
# of participants with ≥ 1 MPA dose steps higher
|
37 study participants
|
30 study participants
|
PRIMARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus).
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Participants With Reduction in Tacrolimus or Tacrolimus Extended Release Levels at the End of the Study (Final Visit) Compared to Baseline Dose.
Reduction in tacrolimus or tacrolimus ER levels
|
27 Participants
|
18 Participants
|
|
Participants With Reduction in Tacrolimus or Tacrolimus Extended Release Levels at the End of the Study (Final Visit) Compared to Baseline Dose.
No reduction in tacrolimus or tacrolimus ER levels
|
16 Participants
|
20 Participants
|
PRIMARY outcome
Timeframe: at 12 months from baselinePopulation: Per protocol (PP) population included all subjects from the ITT population who received medication throughout the study and did not have major protocol deviations and who participated in the study for a minimum of 210 days +/- 15 days
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=29 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=25 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Mean Mycophenolic Acid (MPA) Doses at the End of the Study (Final Visit) Compared to Baseline Dose.
|
1173.10 mg/day
Standard Deviation 278.94
|
1195.20 mg/day
Standard Deviation 297.95
|
SECONDARY outcome
Timeframe: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)Population: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus).
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Baseline (n=42,38)
|
83.01 ml/min
Standard Deviation 26.51
|
83.44 ml/min
Standard Deviation 29.10
|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Visit 1 (n=41,37)
|
81.55 ml/min
Standard Deviation 26.88
|
83.04 ml/min
Standard Deviation 27.06
|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Visit 2 (n=41,34)
|
81.59 ml/min
Standard Deviation 26.60
|
82.88 ml/min
Standard Deviation 24.70
|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Visit 3 (n=37,35)
|
84.91 ml/min
Standard Deviation 24.20
|
80.25 ml/min
Standard Deviation 23.25
|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Visit 4 (n=39,33)
|
86.58 ml/min
Standard Deviation 26.82
|
81.83 ml/min
Standard Deviation 24.89
|
|
Change in Renal Function Measured Using Cockcroft-Gault Creatinine Clearance (CrCl)
Visit 5 (n=36,33)
|
88.08 ml/min
Standard Deviation 26.40
|
88.28 ml/min
Standard Deviation 29.17
|
SECONDARY outcome
Timeframe: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)Population: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus).
Calculated GFR (MDRD formula): GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C is the serum concentration of creatinine \[mg/dL\], A is age \[years\], G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Baseline visit (n=43, 38)
|
64.83 mL/min/1.73m^2
Standard Deviation 17.59
|
61.08 mL/min/1.73m^2
Standard Deviation 13.94
|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Visit 1 (n=42, 38; missings not included)
|
62.68 mL/min/1.73m^2
Standard Deviation 17.68
|
59.78 mL/min/1.73m^2
Standard Deviation 12.32
|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Visit 2 (n=41, 35; missings not included)
|
62.71 mL/min/1.73m^2
Standard Deviation 17.02
|
60.84 mL/min/1.73m^2
Standard Deviation 13.35
|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Visit 3 (n=40, 35; missings not included)
|
67.74 mL/min/1.73m^2
Standard Deviation 18.28
|
59.32 mL/min/1.73m^2
Standard Deviation 13.71
|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Visit 4 (n=42, 36; missings not included)
|
67.21 mL/min/1.73m^2
Standard Deviation 20.19
|
61.20 mL/min/1.73m^2
Standard Deviation 15.78
|
|
Glomerular Filtration Rate (GFR) Using Abbreviated MDRD
Visit 5 (n=38, 35; missings not included)
|
70.24 mL/min/1.73m^2
Standard Deviation 19.23
|
68.11 mL/min/1.73m^2
Standard Deviation 19.84
|
SECONDARY outcome
Timeframe: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)Population: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missings not included
The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Acid reflux (n=42,37)
|
1.40 scores on a scale
Standard Deviation 0.77
|
1.41 scores on a scale
Standard Deviation 0.98
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Hunger pains (n=43,37)
|
2.30 scores on a scale
Standard Deviation 1.52
|
1.92 scores on a scale
Standard Deviation 1.21
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Nausea (n=43,37)
|
1.30 scores on a scale
Standard Deviation 0.99
|
1.35 scores on a scale
Standard Deviation 0.95
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline Visit, Heartburn (n=42,37)
|
1.29 scores on a scale
Standard Deviation 0.92
|
1.54 scores on a scale
Standard Deviation 1.41
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline Visit, Upper Abdomen Pain(n=42,37)
|
1.64 scores on a scale
Standard Deviation 1.08
|
1.70 scores on a scale
Standard Deviation 1.02
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Rumbling in stomach (n=43,37)
|
1.93 scores on a scale
Standard Deviation 1.12
|
1.92 scores on a scale
Standard Deviation 1.36
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Bloated (n=43,37)
|
1.77 scores on a scale
Standard Deviation 1.27
|
2.27 scores on a scale
Standard Deviation 1.71
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Burping (n=43,37)
|
1.91 scores on a scale
Standard Deviation 1.21
|
2.00 scores on a scale
Standard Deviation 1.39
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Passing gas/Flatus (n=43,37)
|
2.19 scores on a scale
Standard Deviation 1.38
|
2.38 scores on a scale
Standard Deviation 1.48
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Constipation (n=42,37)
|
1.71 scores on a scale
Standard Deviation 1.15
|
1.62 scores on a scale
Standard Deviation 1.36
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Diorrhoea (n=42,37)
|
1.45 scores on a scale
Standard Deviation 1.09
|
1.51 scores on a scale
Standard Deviation 1.17
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Loose stool (n=42,37)
|
1.69 scores on a scale
Standard Deviation 1.16
|
1.84 scores on a scale
Standard Deviation 1.38
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Hard stool (n=42,37)
|
1.52 scores on a scale
Standard Deviation 1.04
|
1.65 scores on a scale
Standard Deviation 1.16
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline visit, Fecal incontinence (n=42,37)
|
1.67 scores on a scale
Standard Deviation 1.18
|
2.03 scores on a scale
Standard Deviation 1.69
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Baseline, Incomplete bowel emptying (n=42,37)
|
1.57 scores on a scale
Standard Deviation 0.99
|
1.97 scores on a scale
Standard Deviation 1.36
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Upper Abdomen Pain (n=40,34)
|
1.43 scores on a scale
Standard Deviation 0.75
|
1.74 scores on a scale
Standard Deviation 1.16
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Heartburn (n=40,35)
|
1.43 scores on a scale
Standard Deviation 1.06
|
1.37 scores on a scale
Standard Deviation 0.73
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Acid reflux (n=40,35)
|
1.30 scores on a scale
Standard Deviation 0.76
|
1.57 scores on a scale
Standard Deviation 0.95
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Hunger pains (n=39,34)
|
2.33 scores on a scale
Standard Deviation 1.77
|
2.15 scores on a scale
Standard Deviation 1.33
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Nausea (n=39,34)
|
1.23 scores on a scale
Standard Deviation 0.67
|
1.29 scores on a scale
Standard Deviation 0.76
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Rumbling in stomach (n=39,34)
|
1.85 scores on a scale
Standard Deviation 1.06
|
1.85 scores on a scale
Standard Deviation 1.16
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Bloated (n=40,35)
|
1.73 scores on a scale
Standard Deviation 1.09
|
2.09 scores on a scale
Standard Deviation 1.48
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Burping (n=40,35)
|
1.80 scores on a scale
Standard Deviation 1.11
|
2.00 scores on a scale
Standard Deviation 1.55
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Passing gas/Flatus (n=40,35)
|
2.35 scores on a scale
Standard Deviation 1.42
|
2.34 scores on a scale
Standard Deviation 1.49
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Constipation (n=40,33)
|
1.58 scores on a scale
Standard Deviation 1.13
|
1.52 scores on a scale
Standard Deviation 0.97
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Diorrhoea (n=40,33)
|
1.38 scores on a scale
Standard Deviation 0.84
|
1.82 scores on a scale
Standard Deviation 1.42
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Loose stool (n=40,32)
|
1.73 scores on a scale
Standard Deviation 1.04
|
1.91 scores on a scale
Standard Deviation 1.20
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Hard stool (n=39,35)
|
1.51 scores on a scale
Standard Deviation 1.12
|
1.46 scores on a scale
Standard Deviation 0.82
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Fecal incontinence (n=39,34)
|
1.69 scores on a scale
Standard Deviation 1.30
|
2.12 scores on a scale
Standard Deviation 1.51
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 2, Incomplete bowel emptying (n=39,35)
|
1.67 scores on a scale
Standard Deviation 0.96
|
1.69 scores on a scale
Standard Deviation 1.13
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Upper Abdomen Pain (n=41,34)
|
1.66 scores on a scale
Standard Deviation 1.26
|
2.00 scores on a scale
Standard Deviation 1.30
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Heartburn (n=41,34)
|
1.59 scores on a scale
Standard Deviation 1.24
|
1.74 scores on a scale
Standard Deviation 1.19
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Acid reflux (n=41,34)
|
1.46 scores on a scale
Standard Deviation 1.12
|
1.56 scores on a scale
Standard Deviation 0.99
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Hunger pains (n=41,34)
|
2.00 scores on a scale
Standard Deviation 1.60
|
2.26 scores on a scale
Standard Deviation 1.29
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Nausea (n=41,34)
|
1.37 scores on a scale
Standard Deviation 0.80
|
1.59 scores on a scale
Standard Deviation 1.18
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Rumbling in stomach (n=41,34)
|
2.02 scores on a scale
Standard Deviation 1.09
|
1.91 scores on a scale
Standard Deviation 1.22
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Bloated (n=41,34)
|
1.68 scores on a scale
Standard Deviation 1.04
|
2.15 scores on a scale
Standard Deviation 1.58
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Burping (n=41,34)
|
2.02 scores on a scale
Standard Deviation 1.41
|
2.21 scores on a scale
Standard Deviation 1.47
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Passing gas/Flatus (n=41,34)
|
2.46 scores on a scale
Standard Deviation 1.21
|
2.44 scores on a scale
Standard Deviation 1.48
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Constipation (n=41,34)
|
1.41 scores on a scale
Standard Deviation 0.74
|
1.85 scores on a scale
Standard Deviation 1.42
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Diorrhoea ((n=41,34)
|
1.59 scores on a scale
Standard Deviation 1.26
|
1.88 scores on a scale
Standard Deviation 1.09
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Loose stool (n=41,34)
|
2.00 scores on a scale
Standard Deviation 1.50
|
1.94 scores on a scale
Standard Deviation 1.13
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Hard stool (n=40,34)
|
1.53 scores on a scale
Standard Deviation 0.88
|
1.85 scores on a scale
Standard Deviation 1.26
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Fecal incontinence (n=40,34)
|
1.68 scores on a scale
Standard Deviation 1.29
|
2.12 scores on a scale
Standard Deviation 1.43
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 4, Incomplete bowel emptying(n=40,34)
|
1.68 scores on a scale
Standard Deviation 0.92
|
1.88 scores on a scale
Standard Deviation 1.25
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Upper Abdomen Pain (n=36,34)
|
1.72 scores on a scale
Standard Deviation 1.19
|
1.85 scores on a scale
Standard Deviation 1.28
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Heartburn (n=36,34)
|
1.47 scores on a scale
Standard Deviation 0.94
|
1.56 scores on a scale
Standard Deviation 1.08
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Acid reflux (n=36,34)
|
1.25 scores on a scale
Standard Deviation 0.60
|
1.71 scores on a scale
Standard Deviation 1.14
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Hunger pains (n=36,34)
|
1.94 scores on a scale
Standard Deviation 1.49
|
2.12 scores on a scale
Standard Deviation 2.03
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Nausea (n=36,34)
|
1.28 scores on a scale
Standard Deviation 0.70
|
1.38 scores on a scale
Standard Deviation 0.92
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Rumbling in stomach (n=36,34)
|
2.03 scores on a scale
Standard Deviation 1.13
|
2.00 scores on a scale
Standard Deviation 1.41
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Bloated (n=36,34)
|
1.69 scores on a scale
Standard Deviation 1.12
|
2.12 scores on a scale
Standard Deviation 1.53
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Burping (n=36,34)
|
1.75 scores on a scale
Standard Deviation 1.18
|
2.00 scores on a scale
Standard Deviation 1.50
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Passing gas/Flatus (n=36,34)
|
2.33 scores on a scale
Standard Deviation 1.31
|
2.41 scores on a scale
Standard Deviation 1.60
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Constipation (n=36,34)
|
1.47 scores on a scale
Standard Deviation 0.91
|
1.68 scores on a scale
Standard Deviation 1.01
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Diorrhoea (n=36,34)
|
1.42 scores on a scale
Standard Deviation 1.02
|
1.71 scores on a scale
Standard Deviation 0.91
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Loose stool (n=36,34)
|
1.83 scores on a scale
Standard Deviation 1.23
|
1.74 scores on a scale
Standard Deviation 0.96
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Hard stool (n=36,34)
|
1.36 scores on a scale
Standard Deviation 0.72
|
1.79 scores on a scale
Standard Deviation 1.12
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Fecal incontinence (n=36,34)
|
1.86 scores on a scale
Standard Deviation 1.33
|
2.32 scores on a scale
Standard Deviation 1.70
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Item Score
Visit 5, Incomplete bowel emptying (n=36,34)
|
1.69 scores on a scale
Standard Deviation 1.04
|
1.85 scores on a scale
Standard Deviation 1.18
|
SECONDARY outcome
Timeframe: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)Population: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missings not included
The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Baseline visit, Indigestion (n=43,37)
|
1.95 scores on a scale
Standard Deviation 0.89
|
2.14 scores on a scale
Standard Deviation 1.29
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Baseline visit, Diorrhoea (n=41,37)
|
1.58 scores on a scale
Standard Deviation 0.93
|
1.79 scores on a scale
Standard Deviation 1.26
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Baseline visit, Constipation (n=41,37)
|
1.59 scores on a scale
Standard Deviation 0.91
|
1.75 scores on a scale
Standard Deviation 1.12
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 2, Reflux (n=40,35)
|
1.36 scores on a scale
Standard Deviation 0.81
|
1.47 scores on a scale
Standard Deviation 0.74
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 2, Abdominal pain (n=39,33)
|
1.67 scores on a scale
Standard Deviation 0.71
|
1.71 scores on a scale
Standard Deviation 0.88
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 2, Indigestion (n=39,34)
|
1.92 scores on a scale
Standard Deviation 0.87
|
1.96 scores on a scale
Standard Deviation 1.08
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 2, Diorrhoea (n=39,32)
|
1.59 scores on a scale
Standard Deviation 0.94
|
1.94 scores on a scale
Standard Deviation 1.19
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 2, Constpation (n=39,33)
|
1.59 scores on a scale
Standard Deviation 0.88
|
1.56 scores on a scale
Standard Deviation 0.86
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 4, Reflux (n=41,34)
|
1.52 scores on a scale
Standard Deviation 1.15
|
1.65 scores on a scale
Standard Deviation 1.04
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 4, Abdominal pain (n=41,34)
|
1.67 scores on a scale
Standard Deviation 0.83
|
1.95 scores on a scale
Standard Deviation 1.12
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 4, Indigestion (n=41,34)
|
2.05 scores on a scale
Standard Deviation 0.97
|
2.18 scores on a scale
Standard Deviation 1.27
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 4, Diorrhoea (n=40,34)
|
1.72 scores on a scale
Standard Deviation 1.23
|
1.98 scores on a scale
Standard Deviation 1.08
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 4, Constipation(n=40,34)
|
1.54 scores on a scale
Standard Deviation 0.68
|
1.86 scores on a scale
Standard Deviation 1.12
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 5, Reflux (n=36,34)
|
1.36 scores on a scale
Standard Deviation 0.69
|
1.63 scores on a scale
Standard Deviation 1.06
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 5, Abdominal pain (n=36,34)
|
1.65 scores on a scale
Standard Deviation 0.66
|
1.78 scores on a scale
Standard Deviation 1.03
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 5, Indigestion (n=36,34)
|
1.95 scores on a scale
Standard Deviation 0.95
|
2.13 scores on a scale
Standard Deviation 1.28
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 5, Diorrhoea (n=36,34)
|
1.70 scores on a scale
Standard Deviation 1.02
|
1.92 scores on a scale
Standard Deviation 1.04
|
|
Gastrointestinal Symptom Rating Scale (GSRS) Subscale Score
Visit 5, Constipation (n=36,34)
|
1.51 scores on a scale
Standard Deviation 0.65
|
1.77 scores on a scale
Standard Deviation 0.89
|
SECONDARY outcome
Timeframe: Visit 1 (30 days +/-4), visit 2 (90 days +/- 15), visit 3 (150 days +/- 15), visit 4 (210 days +/- 15), visit 5 (365 days +/- 15)Population: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missings not included
The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=43 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=38 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.
Baseline visit (n=41,37)
|
79.20 scores on a scale
Standard Deviation 6.86
|
76.00 scores on a scale
Standard Deviation 9.55
|
|
Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.
Visit 2 (n=38,32)
|
78.79 scores on a scale
Standard Deviation 6.20
|
76.34 scores on a scale
Standard Deviation 10.12
|
|
Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.
Visit 4 (n=40,34)
|
77.88 scores on a scale
Standard Deviation 6.64
|
74.53 scores on a scale
Standard Deviation 10.24
|
|
Health-related Quality of Life (HRQoL): Impact of Gastrointestinal Symptoms on Quality Of Life (SIGIT)-QoL Questionnaire. Total Score.
Visit 5, Diorrhoea (n=36,34)
|
78.53 scores on a scale
Standard Deviation 5.06
|
76.41 scores on a scale
Standard Deviation 8.36
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=3, 3)
|
1.67 scores on a scale
Standard Deviation 10.50
|
0.00 scores on a scale
Standard Deviation 1.73
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
No SNP present in the UGT1A9 gene (n=18, 25)
|
-0.72 scores on a scale
Standard Deviation 6.52
|
1.52 scores on a scale
Standard Deviation 5.86
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=4, 3)
|
6.25 scores on a scale
Standard Deviation 12.39
|
0.67 scores on a scale
Standard Deviation 2.31
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
No SNP present in the UGT1A9 gene (n=19, 25)
|
1.42 scores on a scale
Standard Deviation 9.06
|
2.96 scores on a scale
Standard Deviation 10.33
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missing not included
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=3,3)
|
8.00 scores on a scale
Standard Deviation 13.86
|
4.00 scores on a scale
Standard Deviation 4.00
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the UGT1A9 Gene for the ITT Population
No SNP present in the UGT1A9 gene (n=20, 23)
|
1.10 scores on a scale
Standard Deviation 9.26
|
-0.48 scores on a scale
Standard Deviation 9.55
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9, 14)
|
1.78 scores on a scale
Standard Deviation 6.65
|
0.79 scores on a scale
Standard Deviation 5.91
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=12, 14)
|
-2.00 scores on a scale
Standard Deviation 6.94
|
1.93 scores on a scale
Standard Deviation 5.36
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9, 14)
|
5.67 scores on a scale
Standard Deviation 11.48
|
3.71 scores on a scale
Standard Deviation 6.23
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=14, 14)
|
0.07 scores on a scale
Standard Deviation 7.79
|
1.71 scores on a scale
Standard Deviation 12.57
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The GSRS is a 15-item instrument design to assess the symptoms associated to gastrointestinal disorders. It has 5 subscales (reflux, diarrhoea, constipation, abdominal pain and indigestion) with scores rating from 1 to 7 (with a higher score representing more gastrointestinal symptoms)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9, 14)
|
3.67 scores on a scale
Standard Deviation 10.17
|
1.92 scores on a scale
Standard Deviation 9.40
|
|
Change in Gastrointestinal Symptom Rating Scale (GSRS) Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of Single-nucleotide Polymorphisms (SNPs) in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=14, 14)
|
0.93 scores on a scale
Standard Deviation 9.88
|
-1.57 scores on a scale
Standard Deviation 8.94
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=4, 3)
|
-5.50 scores on a scale
Standard Deviation 6.45
|
0.33 scores on a scale
Standard Deviation 0.58
|
|
Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
No SNP present in the MRP2 gene (n=18, 28)
|
-0.44 scores on a scale
Standard Deviation 2.81
|
-0.46 scores on a scale
Standard Deviation 5.35
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=4, 3)
|
-5.75 scores on a scale
Standard Deviation 7.41
|
-1.67 scores on a scale
Standard Deviation 2.52
|
|
Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
No SNP present in the UGT1A9 gene (n=19, 27)
|
-2.00 scores on a scale
Standard Deviation 7.14
|
-2.63 scores on a scale
Standard Deviation 8.54
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 Participants
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
SNP present in the UGT1A9 gene (n=3, 3)
|
-1.33 scores on a scale
Standard Deviation 8.39
|
-3.67 scores on a scale
Standard Deviation 6.35
|
|
Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the UGT1A9 Gene for the ITT Population
No SNP present in the UGT1A9 gene (n=20, 26)
|
-0.55 scores on a scale
Standard Deviation 5.45
|
-0.65 scores on a scale
Standard Deviation 7.03
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus)
Sub-study primary endpoint. SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9,16)
|
-0.89 scores on a scale
Standard Deviation 3.79
|
0.56 scores on a scale
Standard Deviation 4.65
|
|
Change in SIGIT-QoL Score From Baseline to Visit 2 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=13, 15)
|
-1.69 scores on a scale
Standard Deviation 4.33
|
-1.40 scores on a scale
Standard Deviation 5.49
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missings not included
Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9,15)
|
-2.67 scores on a scale
Standard Deviation 7.78
|
-1.73 scores on a scale
Standard Deviation 5.40
|
|
Change in SIGIT-QoL Score From Baseline to Visit 4 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=14, 15)
|
-2.64 scores on a scale
Standard Deviation 7.04
|
-3.33 scores on a scale
Standard Deviation 10.29
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: Intention-to-treat (ITT) population included all randomised patients who gave signed informed consent and received at least one dose of study medicinal product and had at least one baseline visit and one post-baseline visit (containing data to allow primary endpoint to be calculated, i.e. dose of MPA or MMF and Tacrolimus). Missing not included
Sub-study primary endpoint. The SIGIT-QoL scale is a 17 items instrument, the score of each item ranges from 0 (always) to 4 (never). The scale score is obtained by adding the scores of the 17 items. Therefore, the total score ranges from 0 to 68 points. Higher score means, less impairment of Health Related QoL of the patient and vice versa, the lower the score, the greater severity of symptoms and worse perceived by the patient
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=24 scores on a scale
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
n=31 scores on a scale
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
SNP present in the MRP2 gene (n=9,14)
|
-1.11 scores on a scale
Standard Deviation 6.86
|
-0.50 scores on a scale
Standard Deviation 7.85
|
|
Change in SIGIT-QoL Score From Baseline to Visit 5 Stratified on the Basis of the Presence or Absence of SNP in the MRP2 Gene for the ITT Population
No SNP present in the MRP2 gene (n=14, 15)
|
-0.36 scores on a scale
Standard Deviation 5.02
|
-1.40 scores on a scale
Standard Deviation 6.17
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: The safety population included all randomised patients who gave signed informed consent and received at least one dose of the study medicinal product.
Exposure to study drug (MPS). Data presented only for safety population on the study treatment arm (not applicable for MMF arm)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=46 Participants
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Duration of Exposure to the Study Medicinal Product, Mycophenolate Sodium Descriptive Statistics. Safety Population Per Treatment Group
|
201.91 days
Standard Deviation 49.00
|
—
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: The safety population included all randomised patients who gave signed informed consent and received at least one dose of the study medicinal product.
Safety population per visit and per treatment group
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=46 patient doses
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)
Baseline visit (n=46)
|
579.13 mg
Standard Deviation 165.03
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)
Visit 1 (n=43)
|
856.28 mg
Standard Deviation 181.65
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)
Visit 2 (n=41)
|
1080.00 mg
Standard Deviation 238.12
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Sodium (MPS)
Visit 3 (n=40)
|
1228.50 mg
Standard Deviation 263.81
|
—
|
SECONDARY outcome
Timeframe: at 12 months from baselinePopulation: The safety population included all randomised patients who gave signed informed consent and received at least one dose of the study medicinal product.
Safety population per visit and per treatment group (missings not included)
Outcome measures
| Measure |
Mycophenolate Sodium (MPS)
n=40 patient doses
Participants continued their treatment with MPS according to normal clinical practice, with the dose of MPS increasing at each visit (visit 1 to visit 3) by 250 mg every 12 h and the dose of tacrolimus or tacrolimus extended release (ER) reducing by 25% (to a minimum level of 4 ng/ml).1 The purpose of dosage adjustments was to establish and maintain the patient on the maximum tolerated dose of MPS (up to a maximum of 1 g every 12 h).
|
Mycophenolate Mofetil (MMF)
Participants were converted to an equimolar dose of Mycophenolate mofetil at baseline visit. Dose of Mycophenolate mofetil was increased at each visit (visits 1 to visit 3) by 180 mg every 12 hours and the tacrolimus or tacrolimus extended release 6 dose was reduced by 25% (to a minimum level of 4 ng/ml). 1 Dosage adjustments allowed the patient to be established and maintained on the maximum tolerated dose of Mycophenolate mofetil (up to a maximum of 720 mg every 12 hours).
|
|---|---|---|
|
Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)
Baseline visit (n=40)
|
806.25 mg
Standard Deviation 222.80
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)
Visit 1 (n=38)
|
1250.00 mg
Standard Deviation 278.75
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)
Visit 2 (n=35)
|
1578.57 mg
Standard Deviation 382.39
|
—
|
|
Dose of the Study Medicinal Product Mycophenolate Mofetil (MMF)
Visit 3 (n=35)
|
1757.14 mg
Standard Deviation 381.01
|
—
|
Adverse Events
Micofenolato Sodium
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
Micofenolato Mofetilo
Serious events: 4 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Micofenolato Sodium
n=46 participants at risk
Micofenolato sodium
|
Micofenolato Mofetilo
n=40 participants at risk
Micofenolato mofetilo
|
|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/46
|
2.5%
1/40
|
|
Gastrointestinal disorders
Diarrhoea
|
2.2%
1/46
|
0.00%
0/40
|
|
Infections and infestations
Escherichia urinary tract infection
|
2.2%
1/46
|
0.00%
0/40
|
|
Infections and infestations
Graft infection
|
0.00%
0/46
|
2.5%
1/40
|
|
Infections and infestations
Human polyomavirus infection
|
0.00%
0/46
|
2.5%
1/40
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/46
|
2.5%
1/40
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.00%
0/46
|
2.5%
1/40
|
Other adverse events
| Measure |
Micofenolato Sodium
n=46 participants at risk
Micofenolato sodium
|
Micofenolato Mofetilo
n=40 participants at risk
Micofenolato mofetilo
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.2%
1/46
|
5.0%
2/40
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
3/46
|
7.5%
3/40
|
|
Gastrointestinal disorders
Dyspepsia
|
6.5%
3/46
|
0.00%
0/40
|
|
General disorders
Fatigue
|
2.2%
1/46
|
5.0%
2/40
|
|
Infections and infestations
Urinary tract infection
|
10.9%
5/46
|
2.5%
1/40
|
|
Investigations
Blood creatinine increased
|
2.2%
1/46
|
5.0%
2/40
|
|
Nervous system disorders
Headache
|
0.00%
0/46
|
5.0%
2/40
|
Additional Information
Novartis
Pharmaceuticals
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Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial; or disclosure of the trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER