Immunosuppression
Conditions
Keywords
Liver transplantation, mycophenolate mofetil, gastrointestinal, adverse effects
Brief summary
The objective of this study is to determine the tolerability and safety of Myfortic in liver transplant patients. Patients receiving CellCept who have GI side effects will have CellCept discontinued and changed to Myfortic (Myfortic is a new drug similar to CellCept, except it is enteric-coated). Our hypothesis is that Myfortic has less GI side effects and will, therefore, be tolerated better than CellCept and also that Myfortic will have a comparable effectiveness to CellCept.
Detailed description
This is a prospective, single center, open-label, safety and tolerability study on the use of Myfortic after liver transplantation. Adult liver transplant patients who are experiencing GI symptoms (nausea, vomiting, diarrhea, abdominal discomfort/pain, dyspepsia) attributable to CellCept are eligible to enter the study. CellCept will be discontinued and replaced with Myfortic. The duration of the study will be 3 months, and during this time, we will assess the incidence and severity of GI adverse events, the incidence and severity of bone marrow suppression (leukopenia), and the incidence of cytomegalovirus (CMV) infection or disease in patients receiving Myfortic.
Interventions
DRUGMyfortic
Myfortic 360mg or 720 mg BID for 90 days.
Sponsors
Novartis Pharmaceuticals
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* ALL patients will be adult liver transplant recipients, males or females, 18-80 years of age * Patients currently receiving tacrolimus or cyclosporine with or without corticosteroids as part of their immunosuppressive regimen * Patients must be receiving CellCept and must have attributable G.I. symptoms (nausea, vomiting, diarrhea, abdominal discomfort/pain, dyspepsia) * Patients must be more than 30 days post-transplant to be eligible * Females of childbearing potential must have a negative serum pregnancy test prior to the inclusion period
Exclusion criteria
* Multi-organ transplant patients * HIV positive patients. * Living-related liver transplant recipients * Pregnant patients * Patients with a history of extra-hepatic malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin * Patients with thrombocytopenia (\<50,000/mm3), with an absolute neutrophil count of \<1,000/mm3 and/or leukocytopenia (\<2,000/mm3), and/or hemoglobin \<7.0 g/dL prior to enrollment * Patients with a G.I. clinical problem at the time of enrollment (e.g. CMV infection or disease, C. difficile colitis, active peptic ulcer disease, gastroenteritis, inflammatory bowel disease) * Presence of clinically significant infection requiring continued therapy or uncontrolled diabetes mellitus * Evidence of drug and/or alcohol abuse * Decisionally impaired subjects who are not medically or mentally capable of providing consent themselves
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS) | screening, 2, 6 and 12 weeks | The gastrointestinal Symptom Rating Scale (GSRS) is a validated scale, the items range from 1= No discomfort at all to 7= Very severe discomfort. The scale ranges from a minimal value of 15 ( No discomfort at all) to a maximum of 105 ( Very severe discomfort) The GSRS contains 15 items, each rated on a seven- point likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items breakdown into the following five scales: abdominal ( Abdominal pain, hunger pains and nausea): reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome ( borborygmus, abdominal distention, eructation and increased flatus) and constipation syndrome (constipation, hard stools and feeling of incomplete evacuation) |
| Number of Participants With Cytomegalovirus Infection or Disease | 12 weeks | — |
| Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | 12 weeks | The GSRS contains 15 items, each rated on a seven- point likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items breakdown into the following five scales: abdominal ( Abdominal pain, hunger pains and nausea): reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome ( borborygmus, abdominal distention, eructation and increased flatus) and constipation syndrome (constipation, hard stools and feeling of incomplete evacuation) The range of the scale for abdominal pain was 3 to 21, reflux 2 to 14, diarrhea 3 to 21, indigestion 4 to 28 and constipation 3 to 21. Higher values represent more severe discomfort. |
Countries
United States
Participant flow
Pre-assignment details
30 participants were screened only 29 participants were enrolled
Participants by arm
| Arm | Count |
|---|---|
| Liver Transplant Subjects All subjects in this study will receive Myfortic 360mg or 720 mg BID for 90 days.
Myfortic: Myfortic 360mg or 720 mg BID for 90 days. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | diarrhea | 1 |
| Overall Study | nausea and upset stomach | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | screen failed | 1 |
Baseline characteristics
| Characteristic | Liver Transplant Subjects |
|---|---|
| Abdominal Pain- screening | 10.7778 units on a scale STANDARD_DEVIATION 5.09399 |
| Age, Continuous | 52.2 years STANDARD_DEVIATION 13 |
| Constipation screening | 7.2000 units on a scale STANDARD_DEVIATION 4.52769 |
| Diarrhea screening | 10.3200 units on a scale STANDARD_DEVIATION 5.57315 |
| Gender Female | 13 Participants |
| Gender Male | 16 Participants |
| Indigestion screening | 12.6800 units on a scale STANDARD_DEVIATION 7.11056 |
| Reflux screening | 5.0000 units on a scale STANDARD_DEVIATION 3.67423 |
| Region of Enrollment United States | 29 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS)
The GSRS contains 15 items, each rated on a seven- point likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items breakdown into the following five scales: abdominal ( Abdominal pain, hunger pains and nausea): reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome ( borborygmus, abdominal distention, eructation and increased flatus) and constipation syndrome (constipation, hard stools and feeling of incomplete evacuation) The range of the scale for abdominal pain was 3 to 21, reflux 2 to 14, diarrhea 3 to 21, indigestion 4 to 28 and constipation 3 to 21. Higher values represent more severe discomfort.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | Abdominal Pain | 10.78 units on a scale | Standard Deviation 5.09 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | Reflux | 2.64 units on a scale | Standard Deviation 1.04 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | Diarrhea | 5.44 units on a scale | Standard Deviation 3.7 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | Indigestion | 7.08 units on a scale | Standard Deviation 3.4 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS) | Constipation | 4.56 units on a scale | Standard Deviation 1.94 |
Primary
Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS)
The gastrointestinal Symptom Rating Scale (GSRS) is a validated scale, the items range from 1= No discomfort at all to 7= Very severe discomfort. The scale ranges from a minimal value of 15 ( No discomfort at all) to a maximum of 105 ( Very severe discomfort) The GSRS contains 15 items, each rated on a seven- point likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items breakdown into the following five scales: abdominal ( Abdominal pain, hunger pains and nausea): reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome ( borborygmus, abdominal distention, eructation and increased flatus) and constipation syndrome (constipation, hard stools and feeling of incomplete evacuation)
Time frame: screening, 2, 6 and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS) | screening | 46.000 units on a scale | Standard Deviation 21.17585 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS) | 2 weeks | 29.0400 units on a scale | Standard Deviation 9.44934 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS) | 6 weeks | 26.2800 units on a scale | Standard Deviation 8.7964 |
| Liver Transplant Subjects | Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS) | 12 weeks | 25.3600 units on a scale | Standard Deviation 8.87356 |
Primary
Number of Participants With Cytomegalovirus Infection or Disease
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liver Transplant Subjects | Number of Participants With Cytomegalovirus Infection or Disease | 0 participants |