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)

NCT01822483 | Completed Phase 4

• 2 other identifiers: CERL080CERL080ABR08T
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Transplantation

Keywords

Renal transplantation; mycophenolic acid; mycophenolate mofetil; mycophenolate sodium; area under the curve

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);

  Baseline; month 6.

• 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

• Evaluate the association of MPA AUC with renal function estimated by MDRD formula.

  Baseline; day one; months 2, 4 and 6.

• Evaluate the MPA_AUC in renal transplant patients converted to mycophenolate sodium (MPS) with equivalent dose of mycophenolate mofetil (MMF).

  Baseline, five days after day one, fourteen days after day one, months 2,4 and 6

• Evaluate the MPA_AUC in renal transplant patients maintained with mycophenolate mofetil (MMF).

  baseline, months 2,4 and 6

Study Arms (2)

Mycophenolate sodium

EXPERIMENTAL

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

Drug: Mycophenolate sodium

Mycophenolate mofetil

ACTIVE COMPARATOR

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

Drug: Mycophenolate mofetil

Interventions

Mycophenolate sodium 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 sodium

Mycophenolate mofetil DRUG

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

Mycophenolate mofetil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Irmandade Santa Casa de Misericórdia de Porto Alegre: lead
• Novartis: collaborator

Study Sites (1)

Irmandade Da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020090, Brazil

Location

Related Publications (3)

• 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.

  PMID: 21190834 BACKGROUND

• 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.

  PMID: 19357111 BACKGROUND

• 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.

  PMID: 20406219 BACKGROUND

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Valter Garcia, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  PRINCIPAL INVESTIGATOR

• Elizete Keitel, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY CHAIR

• Daniela Seelig, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE

  STUDY CHAIR

• Fabiano Klaus, Physician

  IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE

  STUDY CHAIR

• Ronivan Dal Pra, Pharmacist

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• Larissa Pacheco, Pharmacist

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• Bruna Cardoso, Pharmacist

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• Roger Kist, Trainee

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

• Helen Zanetti, Pharmacist

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PHYSICIAN NEPHROLOGY

Study Record Dates

• First Submitted: March 21, 2013
• First Posted: April 2, 2013
• Study Start: April 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 3, 2015

Record last verified: 2015-04

Locations

BR (1)