Renal Transplantation
Conditions
Keywords
Renal Transplantation, Immunosuppression, Renal transplant recipients, Gastrointestinal symptoms associated with MMF therapy
Brief summary
To determine if conversion to enteric coated MPA allows an escalated dose of mycophenolic acid (MPA) to be tolerated in patients experiencing gastrointestinal (GI) symptoms
Interventions
DRUGEnteric-coated Mycophenolate Acid (EC-MPA)
DRUGMycophenolate Mofetil (MMF)
DRUGPlacebo MMF
DRUGPlacebo EC-MPA
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Recipients of first or second cadaveric, living unrelated or living related kidney transplant. * Patients on a reduced daily dose (500mg to 1500mg) of MMF with existing but tolerable and controlled gastrointestinal symptoms. * Recipients who are at least 4 weeks post renal transplantation with stable renal function.
Exclusion criteria
* Multi organ transplant or previous transplant with organ other than kidney * History of GI disorder prior to transplant * Evidence of GI disorder induced by infection, underlying medical condition, or con med other than MMF * Modification of GI med or MMF dose within one week * Evidence of graft rejection, treatment of acute rejection, unstable renal function within 1 week of (baseline) visit Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response (Yes/no) | 6 weeks | The primary variable was the response (yes/no) with positive response being defined as an increase of 360 mg/day enteric-coated mycophenolate acid (MPA)from the baseline daily dose, tolerated and maintained for a 4 week duration until the end of the study (Week 6). Tolerability was defined as the overall assessment of improvement or no change in the intensity of physician assessed gastrointestinal (GI) symptoms at end of study as reported on the physician administered evaluation of GI symptomatology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals | Baseline and week 4 to week 6 | The average daily doses of enteric-coated mycophenolate acid (MPA) and mycophenolate mofetil (MMF) at baseline and during the last 2 weeks of treatment. 1000 mg MMF = 720 mg enteric-coated MPA (MPA equivalent dose). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited in the US from March 2008 to March 2009.
Pre-assignment details
Patients were screened for eligibility. If eligible, willing to participate and provided informed consent, patients were randomized in a blinded fashion to either an equimolar dose of enteric-coated mycophenolate acid (MPA) or remained on the current dose of mycophenolate mofetil (MMF).
Participants by arm
| Arm | Count |
|---|---|
| Enteric-coated Mycophenolate Acid Equimolar dose of enteric-coated mycophenolate acid with mycophenolate mofetil placebo. 1000 mg mycophenolate mofetil = 720 mg enteric-coated mycophenolate acid (MPA equivalent dose). The active and placebo study medications were dispensed in separate bottles identified as Bottle A and Bottle B. | 15 |
| Mycophenolate Mofetil Mycophenolate mofetil therapy with placebo enteric-coated mycophenolate acid. The active and placebo study medications were dispensed in separate bottles identified as Bottle A and Bottle B. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
Baseline characteristics
| Characteristic | Enteric-coated Mycophenolate Acid | Mycophenolate Mofetil | Total |
|---|---|---|---|
| Age Continuous | 51.3 years STANDARD_DEVIATION 12.54 | 49.8 years STANDARD_DEVIATION 12.45 | 50.5 years STANDARD_DEVIATION 12.3 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 15 | 12 / 15 |
| serious Total, serious adverse events | 2 / 15 | 0 / 15 |
Outcome results
Primary
Number of Participants With Response (Yes/no)
The primary variable was the response (yes/no) with positive response being defined as an increase of 360 mg/day enteric-coated mycophenolate acid (MPA)from the baseline daily dose, tolerated and maintained for a 4 week duration until the end of the study (Week 6). Tolerability was defined as the overall assessment of improvement or no change in the intensity of physician assessed gastrointestinal (GI) symptoms at end of study as reported on the physician administered evaluation of GI symptomatology.
Time frame: 6 weeks
Population: Intent to Treat Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enteric-coated Mycophenolate Acid | Number of Participants With Response (Yes/no) | Yes | 10 Participants |
| Enteric-coated Mycophenolate Acid | Number of Participants With Response (Yes/no) | No | 5 Participants |
| Mycophenolate Mofetil | Number of Participants With Response (Yes/no) | Yes | 9 Participants |
| Mycophenolate Mofetil | Number of Participants With Response (Yes/no) | No | 6 Participants |
Secondary
Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals
The average daily doses of enteric-coated mycophenolate acid (MPA) and mycophenolate mofetil (MMF) at baseline and during the last 2 weeks of treatment. 1000 mg MMF = 720 mg enteric-coated MPA (MPA equivalent dose).
Time frame: Baseline and week 4 to week 6
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-coated Mycophenolate Acid | Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals | MMF Baseline Dose (n=15, 15) | 1033.30 mg | Standard Deviation 351.87 |
| Enteric-coated Mycophenolate Acid | Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals | Week 4 to Week 6 (n=13, 14) | 914.5 mg | Standard Deviation 419.85 |
| Mycophenolate Mofetil | Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals | MMF Baseline Dose (n=15, 15) | 1216.7 mg | Standard Deviation 364.33 |
| Mycophenolate Mofetil | Average Daily Doses (mg) of Enteric-coated Mycophenolate Acid (MPA) and Mycophenolate Mofetil (MMF) by Treatment Duration Intervals | Week 4 to Week 6 (n=13, 14) | 1567.6 mg | Standard Deviation 442.55 |