Clinical trial NCT00522548: Myfortic or CellCept Gastrointestinal Effects in African American Kidney Recipients
Official title: Gastrointestinal Adverse Effect Outcomes of De Novo African American Kidney Transplant Recipients Treated With Tacrolimus, Corticosteroids and Mycophenolate Mofetil or Enteric Coated Mycophenolate Sodium
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Transplants and Implants
Keywords: African American
Kidney Transplant
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2007-08-29
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study consisted of 2 parallel active comparator arms.
Primary purpose: TREATMENT

Brief summary: Myfortic (enteric-coated mycophenolate sodium) has been shown to have similar effectiveness to CellCept (mycophenolate mofetil) in preventing rejection in kidney transplant recipients. However, enteric coated mycophenolate sodium has been thought to possibly be associated with fewer gastrointestinal side effects. Mycophenolate mofetil and enteric coated mycophenolate sodium pharmacokinetics (how the drug is absorbed and broken down) have not been well-studied in African American kidney transplant recipients. The investigators are interested in studying enteric coated mycophenolate sodium and mycophenolate mofetil pharmacokinetics and gastrointestinal side effects in African American kidney transplant recipients.

Detailed description: African American patients often experience more gastrointestinal (GI) complications after kidney transplant than Caucasian patients. In addition, African American kidney transplant recipients also experience a higher incidence of acute rejection and have worse outcomes compared with all other ethnic groups. Reasons accounting for these differences are not well understood.

In light of the increased risk of GI complications in African American patients, we will compare in a pilot study, different regimens (described below) that we commonly use in our clinical practice in this population. As part of this study, patients will also fill out a GSRS survey at specified time points to help describe gastrointestinal side effects after transplant.

Pharmacokinetic studies (studies looking at how the drugs are absorbed and broken down) for mycophenolate mofetil or enteric coated mycophenolate sodium have largely been performed in Caucasian populations. There is little information available in African-American patients. This is particularly concerning in the face of the worst clinical outcomes observed after transplantation in African American kidney transplant recipients.

Comparisons: Patients will be randomized to one of two groups

* Group 1: Myfortic (enteric-coated mycophenolate sodium) in combination with Prograf (tacrolimus) or its generic equivalent and corticosteroids
* Group 2: CellCept (mycophenolate mofetil) or its generic equivalent manufactured by Sandoz in combination with Prograf (tacrolimus) or its generic equivalent and corticosteroids

Since toxicity of mycophenolate mofetil and enteric coated mycophenolate sodium may be influenced by pharmacokinetics (studies that look at how the drugs are absorbed and broken down) of these respective drugs, we will compare the pharmacokinetics of enteric coated mycophenolate sodium and mycophenolate mofetil in a subset of patients. This pharmacokinetic data may have the additional valuable benefit of helping to optimize dosing parameters for mycophenolate mofetil and enteric coated mycophenolate sodium in African American kidney transplant patients in the future.

Eligibility criteria: Inclusion Criteria:

* Recipients of a deceased donor or living donor kidney transplant
* Recipients of age greater than 18 years but less than 76 years
* African Americans (self-reported patients of Black African descent who live in the United States)
* Willingness to participate in a randomized, clinical trial, as indicated by signed informed consent
* Patients with a history of gastrointestinal complications including any of the following: a history of diarrhea, constipation, acid reflux, or abdominal pain as reported by the patient
* For women of childbearing age, effective contraception must be used before beginning CellCept or Myfortic, during therapy and 6 weeks after therapy has been discontinued (childbearing women should have a negative serum or urine pregnancy test within 1 week prior to starting CellCept or Myfortic therapy)

Exclusion Criteria:

* Recipients with any prior solid organ transplant (including kidney)
* Recipients receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant
* Recipient age is less than 18 years old or greater than 75 years old
* Recipients who are not African American (self-reported patients of Black African descent who live in the United States)
* Recipients on proton pump inhibitor therapy at the time of initial screening (pre-transplant to 2 days post-transplant)
* Recipients with a gastrointestinal bleed within the past three months
* Recipients who are pregnant or breast feeding
* Recipients with known human immunodeficiency virus (HIV) infection
* Allergy to any of the immunosuppressant medications
* Concurrent investigational medication
* Any medical or psychosocial condition, which, in the opinion of the investigators, would hinder compliance with the study requirements
* Inability or unwillingness of patient to provide informed consent

Primary outcomes:
measure: Gastrointestinal Toxicity Due to Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Formulation Manufactured by Sandoz
timeFrame: 6 months
Secondary outcomes:
measure: The Incidence of the Requirement of Full Dose Proton Pump Inhibitors in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: 6 months
measure: The Incidence of Intolerance (Defined as Transient Dose Reduction or Transient Discontinuation of Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: 6 months
measure: Gastrointestinal Symptom Rating Scale (GSRS) Score Changes From Baseline to 24 Weeks After Transplant in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: baseline (pre-transplant to two days after transplant) and at 6 months after transplant.
measure: The Incidence of the Occurrence of Upper Gastrointestinal Symptoms Per GSRS Scale Ratings in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Formulation Manufactured by Sandoz
timeFrame: 6 months
measure: The Incidence of the Occurrence of Lower Gastrointestinal Symptoms Per GSRS Scale Ratings in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: 6 months
measure: The Incidence of Rejection in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz.
timeFrame: 6 months
measure: Serum Creatinine in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: 6 months
measure: Modification of Diet and Renal Disease (MDRD) Measured Glomerular Filtration Rates in Patients on Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz
timeFrame: 6 months
measure: Pharmacokinetics (Mycophenolic Acid Trough Levels) of Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz in a Sub-set of Patients
timeFrame: 1 and 6 months
measure: Pharmacokinetics (Mycophenolic Acid Maximum Concentration) of Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz in a Sub-set of Patients
timeFrame: 1 and 6 months
measure: Pharmacokinetics (Mycophenolic Acid Area Under the Curve) of Enteric Coated Mycophenolate Sodium or Mycophenolate Mofetil or Its Generic Equivalent Manufactured by Sandoz in a Sub-set of Patients
timeFrame: 1 and 6 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania-Renal Electrolyte and Hypertension Division
name: Roy Bloom, MD
role: PRINCIPAL_INVESTIGATOR
References: