Small Bowel Capsule Endoscopy Findings in Patients Receiving Cellcept®

• ClinicalTrials.gov Identifier: NCT00652834
• Recruitment Status: Completed
• First Posted: April 4, 2008
• Results First Posted: March 4, 2016
• Last Update Posted: March 4, 2016
• Sponsor: University of California, Los Angeles
• Collaborator: Novartis
• Information provided by (Responsible Party): Suphamai Bunnapradist, University of California, Los Angeles

Tracking Information

• First Submitted Date: April 1, 2008
• First Posted Date: April 4, 2008
• Results First Submitted Date: December 2, 2014
• Results First Posted Date: March 4, 2016
• Last Update Posted Date: March 4, 2016
• Study Start Date: April 2009
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 5, 2016)

GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score [ Time Frame: one month ]

The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A higher GSRS indicate worse symptoms and a difference between D30 and last SBCE scores greater or equal to 0.3 can be considered as a clinically significant improvement in the symptoms.

• Original Primary Outcome Measures (submitted: April 3, 2008): This study aims at providing evidence gastrointestinal mucosal findings in patients receiving MMF and improvement of that findings after conversion from MMF to Myfortic® as demonstrated by SBCE. [ Time Frame: one month ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures (submitted: April 3, 2008): To demonstrate the improvement of gastrointestinal symptoms after conversion to Myfortic® from MMF therapy. [ Time Frame: one month ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Small Bowel Capsule Endoscopy Findings in Patients Receiving Cellcept®
• Official Title: Gastrointestinal Mucosal Findings in Patients Receiving Mycophenolic Acid (MPA) as Demonstrated by Small Bowel Capsule Endoscopy (SBCE)
• Brief Summary: The purpose of this study is to learn more about symptoms and gastrointestinal lesions associated with taking myfortic® by switching patients to a delayed release formulation that is developed to alleviate GI symptoms. A comparison of the frequency and severity of GI symptoms observed in patients treated with MMF (cellcept®) after conversion to myfortic® will be measured by using a self-assessed questionnaire called Gastrointestinal Symptom Rating Scale (GSRS). To prove the incidence and improvement of GI lesions in patients treated with MMF (cellcept®) after conversion to myfortic® will be measured by using Small Bowel Capsule Endoscopy (SBCE).
• Detailed Description: Myfortic® recently introduced to the market has shown to be similar to MMF in how effectively it works and how well it is tolerated. Both drugs have the same active ingredient, but they are different in the way that they deliver them to the body. Myfortic® is an advanced, enteric coated formulation of mycophenolate sodium (EC-MPS) that delays the release of the active ingredient, MPA. MPA has more potent effects on the lymphocytes than other cells. This makes for improved GI tolerability of the MPA therapy.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastrointestinal Lesions
• Signs and Symptoms, Digestive

Intervention

• Procedure: Small bowel capsule endoscopy (SBCE)
  SBCE will be performed at Day 2 and Day 30.
  Other Name: PillCamEso
• Drug: myfortic
  switching from mycophenolate mofetil to mycophenolic acid on equimolar basis
  Other Name: EC-MPS

Study Arms

kidney recipients with GI symptoms

This was a four-week study designed to investigate GI mucosal lesions by SBCE in kidney transplant recipients who were using MMF, and to examine the changes in clinical symptoms and intestinal mucosa lesions 30 days after switching over from MMF to EC-MPS. The patient was switched from MMF to EC-MPS (Myfortic) on the equimola basis.

Interventions:

• Procedure: Small bowel capsule endoscopy (SBCE)
• Drug: myfortic

Publications *

• Shaw LM, Sollinger HW, Halloran P, Morris RE, Yatscoff RW, Ransom J, Tsina I, Keown P, Holt DW, Lieberman R, et al. Mycophenolate mofetil: a report of the consensus panel. Ther Drug Monit. 1995 Dec;17(6):690-9. Review.
• Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman AB, Cibrik D, Magee JC, Wolfe RA, Agodoa LY, Kaplan B. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation. 2000 Jun 15;69(11):2405-9.
• Meier-Kriesche HU, Steffen BJ, Hochberg AM, Gordon RD, Liebman MN, Morris JA, Kaplan B. Long-term use of mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection. Am J Transplant. 2003 Jan;3(1):68-73.
• Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf. 2001;24(9):645-63. Review.
• Salvadori M, Holzer H, de Mattos A, Sollinger H, Arns W, Oppenheimer F, Maca J, Hall M; ERL B301 Study Groups. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant. 2004 Feb;4(2):231-6.
• Dimenäs E, Carlsson G, Glise H, Israelsson B, Wiklund I. Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease. Scand J Gastroenterol Suppl. 1996;221:8-13.
• Kleinman L, Faull R, Walker R, Ramesh Prasad GV, Ambuehl P, Bahner U. Gastrointestinal-specific patient-reported outcome instruments differentiate between renal transplant patients with or without GI complications. Transplant Proc. 2005 Mar;37(2):846-9.
• Bunnapradist S, Sampaio MS, Wilkinson AH, Pham PT, Huang E, Kuo HT, Anastasi B, Danovitch GM, Lo SK. Changes in the small bowel of symptomatic kidney transplant recipients converted from mycophenolate mofetil to enteric-coated mycophenolate sodium. Am J Nephrol. 2014;40(2):184-90. doi: 10.1159/000365360. Epub 2014 Sep 2.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 5, 2016): 23
• Original Estimated Enrollment (submitted: April 3, 2008): 20
• Actual Study Completion Date: May 2011
• Actual Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female patients between 18 and 75 years of age.
• 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 who have used MMF at least 10 days and are currently receiving MMF. (up to 3g/day dosage allowed)
• Patients with at least one moderate or severe upper or lower GI complaints.
• Patients' immunosuppressive regimen other than steroids 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. 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 or previous transplant with any other organ different from kidney.
• The presence of a severe GI disorder. History of a significant GI disorder prior to transplant that has remained unchanged since transplant and/or the introduction of MMF will exclude patient.
• 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 women.
• Patients with thrombocytopenia (<75,000/mm3), with an absolute neutrophil count of <1,500/mm3 and/or leukocytopenia (<3,500/mm3), and/or hemoglobin <9.0 g/dL prior to enrollment.
• Presence of clinically significant pyrexia and/or infection requiring continued therapy.
• Evidence of severe liver disease [incl. abnormal liver profile i.e. AST, ALT or total bilirubin = 3 times the upper limit of normal].
• Patients who have any anatomical GI tract defects which have risk of capsule getting stuck such as tumor or previous abdominal surgery.
• Abnormal physical or laboratory findings of clinical significance within 2 weeks of inclusion which would interfere with the objectives of the study.
• Patients with symptoms of significant illness or evidence of current drug and/or alcohol abuse.
• Inability to self-administer the GSRS & OTE questionnaire.
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00652834
• Other Study ID Numbers: 11-001911
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Suphamai Bunnapradist, University of California, Los Angeles
• Study Sponsor: University of California, Los Angeles
• Collaborators: Novartis

Investigators

• Principal Investigator: suphamai bunnapradist, MD; University of California, Los Angeles

• PRS Account: University of California, Los Angeles
• Verification Date: December 2014