A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS)

Renal Transplantation Clinical Trial

— AUC-MPA  

Official title:

A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01822483
• Other study ID #: CERL080
• Secondary ID: CERL080ABR08T
• Status: Completed
• Phase: Phase 4
• First received: March 21, 2013
• Last updated: April 1, 2015
• Start date: April 2013
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Irmandade Santa Casa de Misericórdia de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is investigate mycophenolic acid exposure through area under the curve in renal transplants recipients treated with mycophenolate mofetil and after conversion to mycophenolate sodium.

Description:

A growing body of evidence has shown that mycophenolate acid (MPA) exposure assessment and dosage adjustment are necessary in patients treated with mycophenolate mofetil (MMF), but there is still limited information about the dose-exposure-effect relationship of the enteric-coated mycophenolate sodium (EC-MPS) formulation that has quite different physicochemical properties (TETT et al., 2011).

Pharmacokinetically guided exposure-controlled area under the concentration-time curve (AUC) approaches are helpful to limit interpatient variability of MPA exposure and to improve the clinical outcome of organ transplant recipients (TETT et al., 2011).

MPA area under the concentration-time curve values between 30 and 60 μg h/mL in the early post-transplant period reduces the risk of acute rejections and seems to be appropriate in renal allograft recipients taking mycophenolate sodium (MPS) and calcineurin inhibitors (GRINYÓ et al., 2009; SOMMERER et al., 2010).

Among the benefits of therapeutic drug monitoring of MPA are the evaluation of interaction between MPA and proton pump inhibitors and association of donor-specific antibodies reduction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age = 18 years at the time of screening;

• Subjects above the sixth month post renal transplant;

• Subjects receiving mycophenolate mofetil;

• Women of childbearing potential (CBP) with a negative pregnancy test at screening (urine or serum);

• Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.

Exclusion Criteria:

• Subjects who, in the opinion of the investigator, are not able to complete the study;

• Recipients of multiple organ transplant (i.e., prior or concurrent transplantation of a non-renal allograft;

• Use of any investigational drug or treatment up to 4 weeks before enrollment;

• Subjects with a calculated GFR < 30ml/min (abbreviated MDRD formula);

• Subjects with a screening total white blood cell count (WBC) = 2000/mm3, hemoglobin = 10g/dL and platelet count = 100000/mm3;

• TGO/AST, TGP/ALT and bilirubin with values three times higher that reference values;

• History of malignancy within 3 years enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin;

• Subjects who are known to be human immunodeficiency virus (HIV), hepatitis B or hepatitis C;

• Chronic hepatic failure;

• Planned treatment with immunosuppressive therapies other than those described in the protocol;

• Recipients who required desensitization protocols.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Mycophenolate sodium
The conversion will be performed abruptly for all patients. Mycophenolate mofetil will be discontinued one day before the day of conversion (Day 1). Mycophenolate sodium will be introduced on day 1 with equivalent doses.
• Mycophenolate mofetil
Mycophenolate mofetil dose will be maintained or adjusted to keep 30 to 60 mg*h ml-1.

Locations

Country	Name	City	State
Brazil	Irmandade Da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre	Rio Grande do Sul

Sponsors (2)

Lead Sponsor	Collaborator
Irmandade Santa Casa de Misericórdia de Porto Alegre	Novartis

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Grinyó JM, Ekberg H, Mamelok RD, Oppenheimer F, Sánchez-Plumed J, Gentil MA, Hernandez D, Kuypers DR, Brunet M. The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy. Nephrol Dial Transplant. 2009 Jul;24(7):2269-76. doi: 10.1093/ndt/gfp162. Epub 2009 Apr 8. — View Citation

Sommerer C, Müller-Krebs S, Schaier M, Glander P, Budde K, Schwenger V, Mikus G, Zeier M. Pharmacokinetic and pharmacodynamic analysis of enteric-coated mycophenolate sodium: limited sampling strategies and clinical outcome in renal transplant patients. Br J Clin Pharmacol. 2010 Apr;69(4):346-57. doi: 10.1111/j.1365-2125.2009.03612.x. — View Citation

Tett SE, Saint-Marcoux F, Staatz CE, Brunet M, Vinks AA, Miura M, Marquet P, Kuypers DR, van Gelder T, Cattaneo D. Mycophenolate, clinical pharmacokinetics, formulations, and methods for assessing drug exposure. Transplant Rev (Orlando). 2011 Apr;25(2):47-57. doi: 10.1016/j.trre.2010.06.001. Epub 2010 Dec 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).	Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).	Baseline	No
Secondary	Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);	Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);	Baseline; month 6.	No
Secondary	Evaluate the interaction between MMF or EC-MPS and the proton pump inhibitor omeprazole through the AUC in patients with MPA below target level (30mcg*h ml-1).	Evaluate the interaction between MMF or EC-MPS and the proton pump inhibitor omeprazole through the AUC in patients with MPA below target level (30mcg*h ml-1).	6 months	No
Secondary	Evaluate the association of MPA AUC with renal function estimated by MDRD formula.	Evaluate the association of MPA AUC with renal function estimated by MDRD formula.	Baseline; day one; months 2, 4 and 6.	Yes
Secondary	Evaluate the MPA_AUC in renal transplant patients converted to mycophenolate sodium (MPS) with equivalent dose of mycophenolate mofetil (MMF).	Evaluate the MPA_AUC in renal transplant patients who were taking mycophenolate mofetil (MMF) and were converted to the use of mycophenolate sodium (MPS) by having the MPA concentration below the target level of 30 mcg*h ml-1.	Baseline, five days after day one, fourteen days after day one, months 2,4 and 6	No
Secondary	Evaluate the MPA_AUC in renal transplant patients maintained with mycophenolate mofetil (MMF).	Evaluate the AUC_MPA in renal transplant patients maintained with mycophenolate mofetil(MMF) by having the MPA concentration between 30-60 mcg*h ml-1	baseline, months 2,4 and 6	No