Renal TransplantationPhase 4AUC-MPANCT01822483

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)

A Phase 4 study testing Mycophenolate sodium and Mycophenolate mofetil in people with Renal Transplantation, run by Irmandade Santa Casa de Misericórdia de Porto Alegre at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Renal Transplantation
What is being tested?: Mycophenolate sodium and Mycophenolate mofetil
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 100 participants
Where: 1 siteBrazil
Study dates: Apr 2013to Mar 2015
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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;

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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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Irmandade Da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90020090

Other trials in Brazil

About this study

Read the 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
Being tested: Mycophenolate sodium, Mycophenolate mofetil
Keywords: Renal transplantation, mycophenolic acid, mycophenolate mofetil, mycophenolate sodium, area under the curve

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01822483
Study group	Role	What they receive
Mycophenolate sodium	Experimental	Arm1(Conversion):MPA AUC below 30mcg*h ml-1 - MPS+Calcineurin inhibitor+prednisone Receives: 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 Receives: Drug: Mycophenolate mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Baseline

Secondary outcomes (5)

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);
Measured: 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).
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).
Measured: 6 months
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.
Measured: 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).
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.
Measured: 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).
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
Measured: baseline, months 2,4 and 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2013Mar 2015

First posted2 Apr 2013 (estimated)
Study startApr 2013
Primary completionMar 2015
Study completionMar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Renal TransplantationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01822483
Sponsor's protocol ID: CERL080
Other IDs: CERL080ABR08T
Acronym: AUC-MPA
Status last verified: Apr 2015
First submitted: 21 Mar 2013
Last updated: 3 Apr 2015
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 21190834
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.
PubMed 19357111
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.
PubMed 20406219

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

All Renal Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01822483
Acronym / sponsor ID: AUC-MPA / CERL080
Conditions: Renal Transplantation
Keywords: Renal transplantation, mycophenolic acid, mycophenolate mofetil, mycophenolate sodium, area under the curve
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Irmandade Santa Casa de Misericórdia de Porto AlegreUniversity, hospital or other
Collaborators: Novartis
Study start: Apr 2013
Primary completion: Mar 2015 (actual)
Study completion: Mar 2015 (actual)
First posted: 2 Apr 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Mycophenolate sodium	Experimental	Drug: Mycophenolate sodiumArm1(Conversion):MPA AUC below 30mcg*h ml-1 - MPS+Calcineurin inhibitor+prednisone
Mycophenolate mofetil	Active comparator	Drug: Mycophenolate mofetilArm2(Maintained):MPA AUC between 30 to 60 mg*h ml-1 or above 60 mg - MMF+Calcineurin inhibitor+prednisone

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (11 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Mycophenolate sodiumThe 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.	Drug	Mycophenolate sodium
Mycophenolate mofetilMycophenolate mofetil dose will be maintained or adjusted to keep 30 to 60 mg*h ml-1.	Drug	Mycophenolate mofetil

Primary outcome

Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).
Time frame: Baseline
Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).

5 secondary outcomes

Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);
Time frame: 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).
Time frame: 6 months
Evaluate the association of MPA AUC with renal function estimated by MDRD formula.
Time frame: 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).
Time frame: 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).
Time frame: baseline, months 2,4 and 6

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2015.
Background: PubMed 21190834Tett 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.
Background: PubMed 19357111Grinyo 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.
Background: PubMed 20406219Sommerer 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.

Related trials for Renal Transplantation

Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Valter Garcia, Physician principal investigator

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Elizete Keitel, Physician study chair

IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

Daniela Seelig, Physician study chair

IRMANDADE DA SANTA CASA DE MISERICÓRIDA DE PORTO ALEGRE

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mycophenolate sodium and Mycophenolate mofetil in people with Renal Transplantation, run by Irmandade Santa Casa de Misericórdia de Porto Alegre at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1). (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01822483, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2015.