Renal Transplant
Conditions
Keywords
QoL, GI Side Effects, MPA
Brief summary
This open, multi-center randomized controlled study is designed to investigate the quality of life in patients with mycophenolate mofetil (MMF)-induced gastrointestinal (GI) adverse events after converting to enteric-coated mycophenolate sodium (EC-MPS).
Interventions
DRUGEnteric-Coated Mycophenolate Sodium (EC-MPS)
DRUGMycophenolate Mofetil (MMF)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Received kidney transplant 2. Receiving immunosuppressive regimen that includes MMF 3. Patients with GI side effects on standard MMF doses or patients on reduced dose MMF with existing but tolerated/controlled GI side effects. 4. At least 18 years of age 5. Willing to provide written informed consent 6. Able to meet all study requirements including completing questionnaires and completing four study visits.
Exclusion criteria
1. Patients with GI symptoms assumed or known not to be caused by medroxyprogesterone acetate (MPA) therapy (e.g. oral bisphosphonate induced, infectious diarrhea) 2. Acute rejection \< 1 week prior to study enrollment 3. Woman of child-bearing potential who is planning to become pregnant or is pregnant and/or lactating and who is unwilling to use effective means of contraception 4. Presence of psychiatric illness (i.e., schizophrenia, major depression) that, in the opinion of the site investigator, would interfere with study requirements 5. Undergoing acute medical intervention or hospitalization 6. Any other medical condition that, in the opinion of the site investigator based on recall or chart review, would interfere with completing the study, including, but not limited to, visual problems or cognitive impairment. 7. Receiving any investigational drug or have received any investigational drug within 30 days prior to study enrollment. Additional protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mycophenolic Acid (MPA) Maintenance Treatment | at week 13 (last visit) | The primary assessment was based on the percentage of patients who were maintained at week 13 on a dose at least one dose equivalent greater than at baseline (visit 2/week 1). A dose equivalent was defined as EC-MPS 180 mg/day or MMF 250 mg/day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). | At week 3 and week 13 (last visit) | The GSRS is a 15-item instrument designed to assess the impact of upper and lower GI symptoms. There are five subscales: reflux, diarrhea, constipation, abdominal pain, and indigestion-each of which produces a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). A higher score represents greater impairment of quality of life due to GI symptoms (range from 1 to 7). |
| Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). | At week 3 and week 13 (last visit) | Health-related quality of life (HRQoL)was assessed by the Gastrointestinal Quality of Life Index (GIQLI). The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI also has five different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) producing a total score of the 36 items. Lower scores represent more dysfunction. A higher score represents a better quality of life (range from 0 to 144). |
Countries
United Kingdom
Participant flow
Recruitment details
In total, 135 patients were screened. One patient was not randomized due to an SAE prior to the randomization visit. Out of 134 randomized patients, 5 withdrew before taking study drug. Analysis population: 68 in EC-MPS, 61 in MMF.
Participants by arm
| Arm | Count |
|---|---|
| Enteric-Coated Mycophenolate Sodium (EC-MPS) Oral film-coated gastroresistant tablets containing 360mg or 180mg of mycophenolate sodium. Daily dose decided by the physician, was taken morning and evening. | 68 |
| Mycophenolate Mofetil (MMF) 250 mg capsules or 500 mg tablets of mycophenolate mofetil. Daily dose decided by physician, was taken morning and evening. | 61 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Subj. cond. no longer needs study drug | 0 | 1 |
| Overall Study | Unsatisfactory Therapeutic effect | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Enteric-Coated Mycophenolate Sodium (EC-MPS) | Mycophenolate Mofetil (MMF) | Total |
|---|---|---|---|
| Age, Customized <65 years | 65 participants | 51 participants | 116 participants |
| Age, Customized >=65 years | 3 participants | 10 participants | 13 participants |
| Sex: Female, Male Female | 31 Participants | 25 Participants | 56 Participants |
| Sex: Female, Male Male | 37 Participants | 36 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 68 | 26 / 61 |
| serious Total, serious adverse events | 9 / 68 | 7 / 61 |
Outcome results
Primary
Mycophenolic Acid (MPA) Maintenance Treatment
The primary assessment was based on the percentage of patients who were maintained at week 13 on a dose at least one dose equivalent greater than at baseline (visit 2/week 1). A dose equivalent was defined as EC-MPS 180 mg/day or MMF 250 mg/day.
Time frame: at week 13 (last visit)
Population: The intent-to-treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enteric-Coated Mycophenolate Sodium (EC-MPS) | Mycophenolic Acid (MPA) Maintenance Treatment | 47.06 Percentage of Patients |
| Mycophenolate Mofetil (MMF) | Mycophenolic Acid (MPA) Maintenance Treatment | 16.39 Percentage of Patients |
Secondary
Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS).
The GSRS is a 15-item instrument designed to assess the impact of upper and lower GI symptoms. There are five subscales: reflux, diarrhea, constipation, abdominal pain, and indigestion-each of which produces a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). A higher score represents greater impairment of quality of life due to GI symptoms (range from 1 to 7).
Time frame: At week 3 and week 13 (last visit)
Population: Intention to treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable. In this analysis patients who completed GSRS questionnaire in visit 2 (week 1), visit 3 (week 3) and visit 4 (week 13) were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-Coated Mycophenolate Sodium (EC-MPS) | Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). | Week 3: change in GSRS Total Score (N= 61, 59) | -0.63 Units on a scale | Standard Error 0.139 |
| Enteric-Coated Mycophenolate Sodium (EC-MPS) | Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). | Week 13: change in GSRS Total Score (N= 60, 56) | -0.44 Units on a scale | Standard Error 0.165 |
| Mycophenolate Mofetil (MMF) | Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). | Week 3: change in GSRS Total Score (N= 61, 59) | -0.32 Units on a scale | Standard Error 0.142 |
| Mycophenolate Mofetil (MMF) | Changes in Gastrointestinal (GI) Symptoms as Measured by the Gastrointestinal Symptom Rating Scale (GSRS). | Week 13: change in GSRS Total Score (N= 60, 56) | -0.25 Units on a scale | Standard Error 0.169 |
Secondary
Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI).
Health-related quality of life (HRQoL)was assessed by the Gastrointestinal Quality of Life Index (GIQLI). The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI also has five different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) producing a total score of the 36 items. Lower scores represent more dysfunction. A higher score represents a better quality of life (range from 0 to 144).
Time frame: At week 3 and week 13 (last visit)
Population: Intention to treat (ITT) population consisted of all randomized patients who provided baseline and at least 1 post-baseline assessment of the primary variable. In this analysis patients who completed GIQLI questionnaire in visit 2 (week 1), visit 3 (week 3) and visit 4 (week 13) were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-Coated Mycophenolate Sodium (EC-MPS) | Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). | Week 3: change in GIQLI Total Score (N= 61, 58) | 11.65 Units on a scale | Standard Error 3.47 |
| Enteric-Coated Mycophenolate Sodium (EC-MPS) | Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). | Week 13: change in GIQLI Total Score (N= 60, 56) | 4.84 Units on a scale | Standard Error 4.331 |
| Mycophenolate Mofetil (MMF) | Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). | Week 3: change in GIQLI Total Score (N= 61, 58) | 6.08 Units on a scale | Standard Error 3.549 |
| Mycophenolate Mofetil (MMF) | Changes in Gastrointestinal Symptoms as Measured by the Gastrointestinal Quality of Life Index (GIQLI). | Week 13: change in GIQLI Total Score (N= 60, 56) | 1.77 Units on a scale | Standard Error 4.458 |