Small Bowel Capsule Endoscopy Findings in Patients Receiving Cellcept®

Signs and Symptoms, Digestive Clinical Trial

Official title:

Gastrointestinal Mucosal Findings in Patients Receiving Mycophenolic Acid (MPA) as Demonstrated by Small Bowel Capsule Endoscopy (SBCE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00652834
• Other study ID #: 11-001911
• Status: Completed
• Phase: Phase 4
• First received: April 1, 2008
• Last updated: February 5, 2016
• Start date: April 2009
• Est. completion date: May 2011

Study information

• Verified date: December 2014
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Lesions
• Signs and Symptoms
• Signs and Symptoms, Digestive

Intervention

Procedure:
• Small bowel capsule endoscopy (SBCE)
SBCE will be performed at Day 2 and Day 30.

Drug:
• myfortic
switching from mycophenolate mofetil to mycophenolic acid on equimolar basis

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (8)

Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf. 2001;24(9):645-63. Review. — View Citation

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 N — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score	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.	one month	No