Conversion of CellCept to Myfortic: A Prospective Study in Liver Transplant Recipients

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00336895
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 29
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Immunosuppression	Drug: Myfortic	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Conversion of CellCept to Myfortic: A Prospective Study on the Tolerability and Safety of Myfortic in Liver Transplant Recipients
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liver Transplant Subjects All subjects in this study will receive Myfortic 360mg or 720 mg BID for 90 days.	Drug: Myfortic; Myfortic 360mg or 720 mg BID for 90 days.

Outcome Measures

Primary Outcome Measures

1. 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)

2. Number of Participants With Cytomegalovirus Infection or Disease [12 weeks]

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• University of Pittsburgh
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Michael E de Vera, MD, University of Pittsburgh Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roberto Lopez, MD, Assistant Professor of Surgery, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00336895
• Other Study ID Numbers: CERL080A-US27
• First Posted: Jun 14, 2006
• Last Update Posted: Nov 6, 2016
• Last Verified: Nov 1, 2016

• Keywords provided by Roberto Lopez, MD, Assistant Professor of Surgery, University of Pittsburgh: Liver transplantation; mycophenolate mofetil; gastrointestinal; adverse effects
• Additional relevant MeSH terms: Mycophenolic Acid

Study Results

Participant Flow

Pre-assignment Detail	30 participants were screened only 29 participants were enrolled

Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
Period Title: Overall Study
STARTED	30
COMPLETED	26
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.2 (13.0)
Gender (Count of Participants)
Female	13 44.8%
Male	16 55.2%
Region of Enrollment (participants) [Number]
United States	29 100%
Abdominal Pain- screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.7778 (5.09399)
Reflux screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.0000 (3.67423)
Indigestion screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.6800 (7.11056)
Diarrhea screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.3200 (5.57315)
Constipation screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.2000 (4.52769)

Outcome Measures

1. Primary Outcome

Title	Gastrointestinal Side Effects and Quality of Life (Total Score of GSRS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
Measure Participants	29
screening	46.000 (21.17585)
2 weeks	29.0400 (9.44934)
6 weeks	26.2800 (8.79640)
12 weeks	25.3600 (8.87356)

2. Primary Outcome

Title	Number of Participants With Cytomegalovirus Infection or Disease
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
Measure Participants	29
Number [participants]	0 0%

3. Primary Outcome

Title	Gastrointestinal Side Effects and Quality of Life (-Subscales of GSRS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
Measure Participants	29
Abdominal Pain	10.78 (5.09)
Reflux	2.64 (1.04)
Indigestion	7.08 (3.40)
Diarrhea	5.44 (3.70)
Constipation	4.56 (1.94)

Adverse Events

Time Frame	0-12 weeks
Adverse Event Reporting Description	The protocol specified adverse events including bone marrow suppression, incidence of CMV infection and incidence of acute cellular rejection.
Arm/Group Title	Liver Transplant Subjects
Arm/Group Description	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.
All Cause Mortality
	Liver Transplant Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Liver Transplant Subjects
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	Liver Transplant Subjects
	Affected / at Risk (%)	# Events
Total	0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.