Kidney TransplantationPhase 4NCT00585468
Pharmacokinetic Profile of Myfortic in Combination With Tacrolimus in Fed Versus Fasting State
A Phase 4 study testing Myfortic in people with Kidney Transplantation, run by University of Utah at 1 site in United States.
Trial summary
Literature regarding the effect of food on the pharmacokinetic (PK) profile of enteric-coated mycophenolate sodium combined with tacrolimus and corticosteroid withdrawal is lacking. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Myfortic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Jul 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Renal transplant recipients greater than 18 years of age, who have given written consent
Who cannot join
- Taking medications that may alter the metabolism of tacrolimus or mycophenolate sodium
- Experienced an acute rejection episode prior to the pharmacokinetic profile collection
- Serum creatinine >2 mg/dL
- Neutropenia (Absolute Neutrophil Count < 1.3x10^3/mL)
- Received a previous transplant other than a kidney
- Receiving chronic steroids at time of transplant
- Known hypersensitivity to tacrolimus, mycophenolate mofetil, mycophenolate sodium, mycophenolic acid or any of its excipients
Trial locations and contacts
1 site in 1 country.
United States1 site
Univ of Utah-Solid Organ Transplant
Salt Lake City, Utah, 84119
About this study
Official title: Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol in Combination With Tacrolimus in Stable Renal Transplant Recipients in the Fed and Fasting State
Literature regarding the effect of food on the pharmacokinetic (PK) profile of enteric-coated mycophenolate sodium combined with tacrolimus and corticosteroid withdrawal is lacking. The objective of this study is to identify pharmacokinetic variables of mycophenolate sodium (Myfortic®) in the fed and fasting state in stable renal transplant patients on tacrolimus in combination with a rapid steroid withdrawal protocol.
Read the detailed description
Mycophenolate sodium (Myfortic®) is an antiproliferative immunosuppressant used in renal transplantation. Mycophenolate sodium is formulated as an enteric coated tablet that releases mycophenolic acid (MPA) which in turn inhibits inosine monophosphate dehydrogenase (IMPDH). Through inhibition of IMPDH, the de novo pathway of purine synthesis, which T and B lymphocytes rely on for proliferation, is blocked. The pharmacokinetic profile of mycophenolate sodium has mainly been studied in combination with cyclosporine and steroids. There is little information on the pharmacokinetics of mycophenolate sodium in combination with tacrolimus and currently no published information in steroid withdrawal. All current published data on the pharmacokinetics of MPA have been in patients receiving chronic corticosteroids as part of their immunosuppression regimen. As immunosuppression minimization, and especially corticosteroid withdrawal, become more popular it is important to understand how mycophenolate sodium and its metabolites behave in a two-drug maintenance immunosuppression regimen. The study will assess the pharmacokinetic profile of mycophenolate sodium in patients on tacrolimus dose adjusted based on levels, and a steroid withdrawal protocol.
Renal transplant patients will act as their own controls in a randomized crossover design with pharmacokinetic profiles occurring at two different time points. Immunosuppression will consist of induction therapy with maintenance immunosuppression consisting of tacrolimus plus mycophenolate sodium. Corticosteroids will be withdrawn per institutional protocol within the first week post transplant.
Approximately 3-4 weeks post transplant, patients that met enrollment criteria and have consented to participate in the study will be instructed to take 720 milligrams of mycophenolate sodium orally twice daily for one week either separated from food by two hours (fasting state) or with a meal (fed state). After one week, patients will be admitted for approximately 24 hours where they will continue to receive mycophenolate sodium with or without food. During this period, blood samples will be drawn at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours following the dose to evaluate levels of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG). After 24 hours, patients will be discharged with instructions to take mycophenolate sodium in the opposite manner (fed or fasting state) than they had the week before. At the end of the second week the patients will return for a second PK evaluation with blood collection at the same time points following mycophenolate sodium dosing.
- Conditions
- Kidney Transplantation
- Being tested
- Myfortic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MyforticDrug
Also called mycophenolate sodium, mycophenolic acid
Myfortic 720 mg orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| Myfortic - Fed State | Experimental | Mycophenolate sodium taken with a meal. Receives: Drug: Myfortic |
| Myfortic - Fasting State | Experimental | Mycophenolate sodium taken separately from food by 2 hours. Receives: Drug: Myfortic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid (MPA)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid (MPA)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid (MPA)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Area Under the Curve (AUC) From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid (MPA)
AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid Glucuronide (MPAG)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid Glucuronide (MPAG)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid Glucuronide (MPAG)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Area Under the Curve From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid Glucuronide (MPAG)
AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)
Measured: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2008 (estimated)
- Study startDec 2007
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fuad Shihab, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00585468
- Sponsor's protocol ID
- 15121
- Other IDs
- Award# CERL080AUS33
- Status last verified
- Apr 2016
- First submitted
- 21 Dec 2007
- Last updated
- 6 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Arns W, Breuer S, Choudhury S, Taccard G, Lee J, Binder V, Roettele J, Schmouder R. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant. 2005 Apr;19(2):199-206. doi: 10.1111/j.1399-0012.2004.00318.x.
PubMed 15740555Kaplan B, Meier-Kriesche HU, Minnick P, Bastien MC, Sechaud R, Yeh CM, Balez S, Picard F, Schmouder R. Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium. Clin Transplant. 2005 Aug;19(4):551-8. doi: 10.1111/j.1399-0012.2005.00387.x.
PubMed 16008604Zucker K, Rosen A, Tsaroucha A, de Faria L, Roth D, Ciancio G, Esquenazi V, Burke G, Tzakis A, Miller J. Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings. Transpl Immunol. 1997 Sep;5(3):225-32. doi: 10.1016/s0966-3274(97)80042-1.
PubMed 9402690van Gelder T, Klupp J, Barten MJ, Christians U, Morris RE. Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit. 2001 Apr;23(2):119-28. doi: 10.1097/00007691-200104000-00005.
PubMed 11294511
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol in Combination With Tacrolimus in Stable Renal Transplant Recipients in the Fed and Fasting State
- ClinicalTrials.gov ID
- NCT00585468
- Acronym / sponsor ID
- 15121
- Conditions
- Kidney Transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Dec 2007
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 3 Jan 2008 (estimated)
- Results
- Posted 6 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Literature regarding the effect of food on the pharmacokinetic (PK) profile of enteric-coated mycophenolate sodium combined with tacrolimus and corticosteroid withdrawal is lacking. The objective of this study is to identify pharmacokinetic variables of mycophenolate sodium (Myfortic®) in the fed and fasting state in stable renal transplant patients on tacrolimus in combination with a rapid steroid withdrawal protocol.
Detailed description
Mycophenolate sodium (Myfortic®) is an antiproliferative immunosuppressant used in renal transplantation. Mycophenolate sodium is formulated as an enteric coated tablet that releases mycophenolic acid (MPA) which in turn inhibits inosine monophosphate dehydrogenase (IMPDH). Through inhibition of IMPDH, the de novo pathway of purine synthesis, which T and B lymphocytes rely on for proliferation, is blocked. The pharmacokinetic profile of mycophenolate sodium has mainly been studied in combination with cyclosporine and steroids. There is little information on the pharmacokinetics of mycophenolate sodium in combination with tacrolimus and currently no published information in steroid withdrawal. All current published data on the pharmacokinetics of MPA have been in patients receiving chronic corticosteroids as part of their immunosuppression regimen. As immunosuppression minimization, and especially corticosteroid withdrawal, become more popular it is important to understand how mycophenolate sodium and its metabolites behave in a two-drug maintenance immunosuppression regimen. The study will assess the pharmacokinetic profile of mycophenolate sodium in patients on tacrolimus dose adjusted based on levels, and a steroid withdrawal protocol.
Renal transplant patients will act as their own controls in a randomized crossover design with pharmacokinetic profiles occurring at two different time points. Immunosuppression will consist of induction therapy with maintenance immunosuppression consisting of tacrolimus plus mycophenolate sodium. Corticosteroids will be withdrawn per institutional protocol within the first week post transplant.
Approximately 3-4 weeks post transplant, patients that met enrollment criteria and have consented to participate in the study will be instructed to take 720 milligrams of mycophenolate sodium orally twice daily for one week either separated from food by two hours (fasting state) or with a meal (fed state). After one week, patients will be admitted for approximately 24 hours where they will continue to receive mycophenolate sodium with or without food. During this period, blood samples will be drawn at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours following the dose to evaluate levels of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG). After 24 hours, patients will be discharged with instructions to take mycophenolate sodium in the opposite manner (fed or fasting state) than they had the week before. At the end of the second week the patients will return for a second PK evaluation with blood collection at the same time points following mycophenolate sodium dosing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Myfortic - Fed State | Experimental | Drug: MyforticMycophenolate sodium taken with a meal. |
| Myfortic - Fasting State | Experimental | Drug: MyforticMycophenolate sodium taken separately from food by 2 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Renal transplant recipients greater than 18 years of age, who have given written consent
Key exclusion criteria (7 listed)
- Taking medications that may alter the metabolism of tacrolimus or mycophenolate sodium
- Experienced an acute rejection episode prior to the pharmacokinetic profile collection
- Serum creatinine >2 mg/dL
- Neutropenia (Absolute Neutrophil Count < 1.3x10^3/mL)
- Received a previous transplant other than a kidney
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 |
|---|---|---|
| MyforticAlso: mycophenolate sodium, mycophenolic acidMyfortic 720 mg orally twice daily | Drug | Myfortic - Fasting State, Myfortic - Fed State |
Primary outcome
Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid (MPA)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid (MPA)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid (MPA)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Area Under the Curve (AUC) From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid (MPA)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)
Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid Glucuronide (MPAG)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid Glucuronide (MPAG)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid Glucuronide (MPAG)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
Area Under the Curve From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid Glucuronide (MPAG)
Time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15740555Arns W, Breuer S, Choudhury S, Taccard G, Lee J, Binder V, Roettele J, Schmouder R. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant. 2005 Apr;19(2):199-206. doi: 10.1111/j.1399-0012.2004.00318.x.
- Background: PubMed 16008604Kaplan B, Meier-Kriesche HU, Minnick P, Bastien MC, Sechaud R, Yeh CM, Balez S, Picard F, Schmouder R. Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium. Clin Transplant. 2005 Aug;19(4):551-8. doi: 10.1111/j.1399-0012.2005.00387.x.
- Background: PubMed 9402690Zucker K, Rosen A, Tsaroucha A, de Faria L, Roth D, Ciancio G, Esquenazi V, Burke G, Tzakis A, Miller J. Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings. Transpl Immunol. 1997 Sep;5(3):225-32. doi: 10.1016/s0966-3274(97)80042-1.
- Background: PubMed 11294511van Gelder T, Klupp J, Barten MJ, Christians U, Morris RE. Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit. 2001 Apr;23(2):119-28. doi: 10.1097/00007691-200104000-00005.
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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.
Fuad Shihab, MD principal investigator
University of Utah
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 Myfortic in people with Kidney Transplantation, run by University of Utah at 1 site in United States.
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 1 inclusion and 7 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 6 May 2016. 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 United States. 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?
Yes. Results are posted in the registry (first posted 6 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid (MPA) (time frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose). The study lists 8 primary outcomes in all. 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 NCT00585468, which also lists 4 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 6 May 2016.