Enteric-coated Mycophenolate Sodium (EC-MPS) and Mycophenolate Mofetil (MMF) in Renal Transplant Patients With Gastrointestinal (GI) Intolerance

Renal Transplantation Clinical Trial

Official title:

A 4-week, Multicenter, Double-blind, Double-dummy, Randomized, Parallel Group Study to Compare the Gastrointestinal Safety and Tolerability of EC-MPS & MMF When Administered in Combination With Calcineurin Inhibitors in Renal Transplant Recipients Experiencing Gastrointestinal Intolerance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00400400
• Other study ID #: CERL080AUS51
• Status: Completed
• Phase: Phase 4
• First received: November 15, 2006
• Last updated: July 14, 2011
• Start date: October 2006

Study information

• Verified date: July 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Treatment with the immunosuppressive drug mycophenolate mofetil (MMF) may result in gastrointestinal (GI) complications in some patients. This study will investigate the safety and tolerability of converting kidney transplant recipients with gastrointestinal symptoms from their current treatment of mycophenolate mofetil (MMF) to treatment with enteric-coated mycophenolate sodium (EC-MPS).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• Males and females aged 18-75 years, Recipients of first or second cadaveric, living unrelated or living related kidney transplant

• Recipients who are at least 4 weeks post renal transplantation with stable renal function, Patients currently receiving MMF (all dosages are allowed) and either cyclosporine USP (MODIFIED) or tacrolimus with or without corticosteroids as part of their immunosuppressive regimen for at least 2 weeks prior to study start

• Patients with at least one mild and/or moderate and/or severe upper or lower gastrointestinal (GI) complaints clearly associated with MMF therapy as determined by the treating physician. Additional mild GI complaints may coexist

• Patients' immunosuppressive regimen other than steroids (doses and type) as well as medication for treatment of GI symptoms must be unchanged for at least 1 week prior to study start

• Females of childbearing potential must have a negative pregnancy test prior to the inclusion period. The test should be performed locally at Baseline visit. If positive, the patient will not be included. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication

• Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion criteria:

• Multi-organ transplant patients (e.g. kidney and pancreas) or previous transplant with any other organ different from kidney (second kidney transplant is allowed)

• History of GI disorder (diarrhea, Gastroesophageal Reflux Disease (GERD), dyspepsia, Inflammatory Bowel Disease (IBD) or Irritable Bowel Syndrome (IBS) prior to transplantation

• Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MMF, Modification of GI medication or MMF dose within last 1 week

• Evidence of graft rejection, treatment of acute rejection, or unstable renal function within 4 weeks prior to the Baseline visit, Patients who have received an investigational immunosuppressive drug within 4 weeks prior to study entry

• Patients with a history of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin

• Pregnant or nursing (lactating) women, Women of child-bearing potential (WOCBP) not using an acceptable method of contraception such as: surgical sterilization, hormonal contraception, or double-barrier methods.

• Contraception should be maintained throughout the study and for 4 weeks after study drug discontinuation.

Other protocol defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Enteric-coated mycophenolate sodium (EC-MPS)
Enteric-coated mycophenolate sodium supplied as 180 mg tablets.
• Mycophenolate mofetil
Mycophenolate mofetil supplied as 250 mg capsules.
• Placebo to mycophenolate sodium
Placebo to mycophenolate sodium matching tablets.
• Placebo to mycophenolate mofetil
Placebo to mycophenolate mofetil matching capsules.

Locations

Country	Name	City	State
United States	Piedmont Hospital	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Mid-Atlantic Nephrology Associates	Baltimore	Maryland
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	CRSTI	Dallas	Texas
United States	Denver Nephrology	Denver	Colorado
United States	University of Colorado Health Science Center	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	St. John Hospital Medical Center	Detroit	Michigan
United States	Baylor All Saints	Fort Worth	Texas
United States	University of Florida College of Medicine	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	East Carolina University	Greenville	North Carolina
United States	Pinnacle Health at Harrisburg Hospital	Harrisburg	Pennsylvania
United States	Clarian Health Partners	Indianapolis	Indiana
United States	St. Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Univ of KS Medical Ctr	Kansas City	Kansas
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	St. Baranabas Medical Center	Livingston	New Jersey
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	National Institute of Transplantation	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	The University of Tennessee Health Science Center	Memphis	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University Transplantation	New Haven	Connecticut
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	AKDHC Medical Research Services, LLC	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Hospitals and Clinics	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California
United States	University of California, San Diego	San Diego	California
United States	University of California	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Northwest Louisiana Nephrology Research	Shreveport	Louisiana
United States	WKHS/LSUHSC Regional Transplant Center	Shreveport	Louisiana
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Washington Hospital Transplant Research	Washington	District of Columbia
United States	Wake Forest	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants Who Responded to the Conversion to Mycophenolate Sodium (EC-MPS) Therapy	Response assessed using the Gastrointestinal Symptom Rating Scale (GSRS), designed to assess common symptoms with gastrointestinal (GI) disorders. The GSRS has 5 subscales (reflux, diarrhea, constipation, abdominal pain and indigestion) producing a mean subscale score ranging from 1 (no discomfort) to 7 (very severe discomfort). The total score is an average of scores across all 15 items; a higher score indicates more GI symptoms. Response was defined as Day 30 improvement in the GSRS Total Score (change from baseline) of greater than or equal to 0.3. Minimum score is 1; maximum score is 7.	Baseline, Day 30	Yes
Secondary	Number of Participants With Biopsy-proven Acute Rejection (BPAR) and Treated Acute Rejection (TAR)	TAR was defined as an episode of acute rejection that was suspected on clinical grounds and was treated and confirmed by the investigator according to the patient's response to therapy.; BPAR was defined a treated acute rejection that was confirmed by biopsy. A graft core biopsy was performed before or within 24 hours of initiation of anti-rejection therapy and was assessed by the pathologist at the center according to the BANFF 1997 criteria.	30 days	No
Secondary	Change From Baseline to Day 30 in the Severity of Gastrointestinal Symptoms Overall Total Score	The Severity Score for each GI symptom for each participant was calculated based on the physician's evaluation of current GI symptoms recorded at Baseline and Day 30. For each of the 16 individual GI symptoms the severity score ranged from 0 (absent) to 3 (severe). The Overall Total Score is the Mean of severity ratings of the 16 individual symptoms.	Baseline, Day 30	Yes
Secondary	Number of Participants With Reported Dose Changes or Interruption of Study Medication During the 30 Days of Treatment	The number of participants with reported dose changes or interruption of study medication during the 30 days of treatment.The most common dose adjustments were dose increases back to baseline levels following a decrease or interruption and decreases due to abnormal laboratory value Adverse Events (leucopenia, thrombocytopenia, neutropenia, or anemia).	30 days	No
Secondary	Change From Baseline in Lower and Upper GI Symptom Burden Measured by GI Symptom Rating Scale Score	This is reflected by the total score. The total score incorporates lower and upper GI elements. GSRS overall score is the mean of 15 individual GI symptom scores, each rated on a 7- point scale: 1 = no discomfort, 2= minor discomfort, 3 = mild discomfort, 4 = moderate discomfort, 5 = moderately sever discomfort, 6 = severe discomfort and 7 = very severe discomfort. Change from Baseline was calculated using ANCOVA, model includes GSRS, center and treatment group.	Baseline, Day 30	No
Secondary	Change in Gastrointestinal Symptom Rating Scale Subscale Scores After 30 Days of Treatment	The GSRS has five subscales (reflux, diarrhea, constipation, abdominal pain, indigestion) producing a mean subscale score ranging from 1 (=no discomfort at all) to 7 (very severe discomfort). The mean score at baseline (BL), the mean score at Day 30 and the mean Change from BL to Day 30 is presented for each of the five subscales.	Baseline to Day 30	No
Secondary	Change From Baseline (BL) to Day 30 in the Gastrointestinal Quality of Life Index (GIQLI) Total Score and Subscale Scores	The GIQLI is a 36-item questionnaire to assess the impact of GI disease on daily life. The GIQLI has 5 different subscales (GI symptoms, emotional status, physical and social functions, and stress of medical treatment) that are rated on a 5-point scale from 0 to 4. The individual scores are summed to produce a total score of the 36 items for a total possible score of 0 to 144. Lower scores represent greater dysfunction.	Baseline, Day 30	No