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)

NCT ID: NCT01822483

Last Updated: 2015-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-03-31

Brief 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.

Detailed 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.

Conditions

Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Mycophenolate sodium

Arm1(Conversion):MPA AUC below 30mcg\*h ml-1 - MPS+Calcineurin inhibitor+prednisone

Group Type: EXPERIMENTAL

Mycophenolate sodium

Intervention Type: DRUG

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

Arm2(Maintained):MPA AUC between 30 to 60 mg\*h ml-1 or above 60 mg - MMF+Calcineurin inhibitor+prednisone

Group Type: ACTIVE_COMPARATOR

Mycophenolate mofetil

Intervention Type: DRUG

Mycophenolate mofetil dose will be maintained or adjusted to keep 30 to 60 mg\*h ml-1.

Interventions

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.

Intervention Type: DRUG

Mycophenolate mofetil

Mycophenolate mofetil dose will be maintained or adjusted to keep 30 to 60 mg\*h ml-1.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Irmandade Santa Casa de Misericórdia de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Valter Duro Garcia

PHYSICIAN NEPHROLOGY

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Valter Garcia, Physician

Role: PRINCIPAL_INVESTIGATOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Elizete Keitel, Physician

Role: STUDY_CHAIR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Daniela Seelig, Physician

Role: STUDY_CHAIR

IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE

Fabiano Klaus, Physician

Role: STUDY_CHAIR

IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE

Ronivan Dal Pra, Pharmacist

Role: STUDY_DIRECTOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Larissa Pacheco, Pharmacist

Role: STUDY_DIRECTOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Bruna Cardoso, Pharmacist

Role: STUDY_DIRECTOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Roger Kist, Trainee

Role: STUDY_DIRECTOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Helen Zanetti, Pharmacist

Role: STUDY_DIRECTOR

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Locations

Irmandade Da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 21190834 (View on PubMed)

Grinyo JM, Ekberg H, Mamelok RD, Oppenheimer F, Sanchez-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.

Reference Type: BACKGROUND

PMID: 19357111 (View on PubMed)

Sommerer C, Muller-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.

Reference Type: BACKGROUND

PMID: 20406219 (View on PubMed)

Other Identifiers

CERL080ABR08T

Identifier Type: OTHER

Identifier Source: secondary_id

CERL080

Identifier Type: -

Identifier Source: org_study_id