Drug Interaction PotentiationPhase 4NCT02077556
Effect of Everolimus on the Pharmacokinetics of Tacrolimus in Renal Transplant Patients
A Phase 4 study testing Everolimus, Mycophenolate mofetil and Tacrolimus in people with Drug Interaction Potentiation, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The purpose of this study is to understand the effects of everolimus on tacrolimus pharmacokinetics (pk) in patients receiving de novo kidney transplants. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Drug Interaction Potentiation
- What is being tested?
- Everolimus, Mycophenolate mofetil and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2014to 15 Jan 2019
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- De novo kidney transplants
- 20 - 65 years old
- aspartate aminotransferase/alanine aminotransferase within 2 times the upper limit of normal range
Who cannot join
- Pregnancy
- Tuberculosis
- Hepatitis B or C carrier status
- Human immunodeficiency virus-positive status
- Retransplantation or multiorgan transplantation
- History of rheumatoid arthritis
- Use of drugs that might have enhanced or inhibited CYP3A4 or P-gp activity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Everolimus on the Pharmacokinetics of Tacrolimus in Renal Transplant Patients, and the Effect of ABCB1、CYP3A4、CYP3A5、PORGenetic Polymorphism on the Two Drugs
The purpose of this study is to understand the effects of everolimus on tacrolimus pharmacokinetics (pk) in patients receiving de novo kidney transplants.
Read the detailed description
Multidrug immunosuppression regimens have synergistic effects which allow the use of lower doses of individual agents. These regimens generally include calcineurin inhibitors (CNIs: cyclosporine or tacrolimus), mammalian target of rapamycin (mTOR) inhibitors (everolimus or sirolimus), and corticosteroids. CNIs and mTOR inhibitors are substrates for cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp); in addition, cyclosporine is a inhibitor of CYP3A4 and P-gp. Therefore, concomitant administration of those drugs may alter their serum levels.
It is remained to be evaluated whether the pharmacokinetics or clinical efficacy of tacrolimus will be affected when the regimens contain everolimus in clinical practice and the effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs. Mycophenolate mofetil (MMF) has no effect on pharmacokinetics of tacrolimus; therefore, MMF is used as a control to understand the effects of everolimus on pharmacokinetics of tacrolimus in patients receiving de novo kidney transplants. The effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs was also assessed.
- Conditions
- Drug Interaction Potentiation
- Being tested
- Everolimus, Mycophenolate mofetil, Tacrolimus, Methylprednisolone, Prednisolone
- Keywords
- tacrolimus, everolimus, pharmacokinetics, drug interaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican
Everolimus: 1 mg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 3-8 ng/mL
Also called CellCept
Mycophenolate mofetil: 10-15 mg/kg orally every 12 hours from post-operation day 1 (decrease 50% dose if white blood cell < 4000/mcL)
TacrolimusDrug
Also called Prograf
Tacrolimus: 0.05-0.075 mg/kg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 8-12 ng/mL
Also called Solu-Medrol
Methylprednisolone: 50 mg iv every 6 hours on post-operation day 1, 40 mg iv every 6 hours on post-operation day 2, 30 mg iv every 6 hours on post-operation day 3, 20 mg iv every 6 hours on post-operation day 4, 20 mg iv every 8 hours on post-operation day 5, 20 mg iv every 12 hours on post-operation day 6, 20 mg iv on post-operation day 7
PrednisoloneDrug
Also called Predonine
Prednisolone: 20 mg orally once a day from post-operation day 8 to post-operation week 4, then titrated gradually
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Everolimus/Tacrolimus/Methylprednisolone \& Prednisolone Receives: Drug: Everolimus; Drug: Tacrolimus; Drug: Methylprednisolone; Drug: Prednisolone |
| Mycophenolate mofetil | Active comparator | Mycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone Receives: Drug: Mycophenolate mofetil; Drug: Tacrolimus; Drug: Methylprednisolone; Drug: Prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic profiles
Pharmacokinetic parameters include the maximum concentration, trough concentration, area under the whole-blood concentration-time curve between 0 and 12 hours, time to maximum concentration, volume of distribution at steady state, and clearance at steady state.
Measured: Post-operation day 8-10
Secondary outcomes (1)
Acute rejection
Measured: Within the first 2 weeks post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startApr 2014
- Primary completion15 Jan 2019
- Study completion15 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Interaction PotentiationStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Meng-Kun Tsai, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02077556
- Sponsor's protocol ID
- 201312011MINA
- Status last verified
- Jul 2018
- First submitted
- 2 Mar 2014
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Everolimus on the Pharmacokinetics of Tacrolimus in Renal Transplant Patients, and the Effect of ABCB1、CYP3A4、CYP3A5、PORGenetic Polymorphism on the Two Drugs
- ClinicalTrials.gov ID
- NCT02077556
- Acronym / sponsor ID
- 201312011MINA
- Conditions
- Drug Interaction Potentiation
- Keywords
- tacrolimus, everolimus, pharmacokinetics, drug interaction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- 15 Jan 2019 (actual)
- Study completion
- 15 Jan 2019 (actual)
- First posted
- 4 Mar 2014 (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.
The purpose of this study is to understand the effects of everolimus on tacrolimus pharmacokinetics (pk) in patients receiving de novo kidney transplants.
Detailed description
Multidrug immunosuppression regimens have synergistic effects which allow the use of lower doses of individual agents. These regimens generally include calcineurin inhibitors (CNIs: cyclosporine or tacrolimus), mammalian target of rapamycin (mTOR) inhibitors (everolimus or sirolimus), and corticosteroids. CNIs and mTOR inhibitors are substrates for cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp); in addition, cyclosporine is a inhibitor of CYP3A4 and P-gp. Therefore, concomitant administration of those drugs may alter their serum levels.
It is remained to be evaluated whether the pharmacokinetics or clinical efficacy of tacrolimus will be affected when the regimens contain everolimus in clinical practice and the effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs. Mycophenolate mofetil (MMF) has no effect on pharmacokinetics of tacrolimus; therefore, MMF is used as a control to understand the effects of everolimus on pharmacokinetics of tacrolimus in patients receiving de novo kidney transplants. The effect of ABCB1、CYP3A4、CYP3A5、POR genetic polymorphism on the two Drugs was also assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: Everolimus, Drug: Tacrolimus, Drug: Methylprednisolone, Drug: PrednisoloneEverolimus/Tacrolimus/Methylprednisolone \& Prednisolone |
| Mycophenolate mofetil | Active comparator | Drug: Mycophenolate mofetil, Drug: Tacrolimus, Drug: Methylprednisolone, Drug: PrednisoloneMycophenolate mofetil/Tacrolimus/ Methylprednisolone \& Prednisolone |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- De novo kidney transplants
- 20 - 65 years old
- aspartate aminotransferase/alanine aminotransferase within 2 times the upper limit of normal range
Key exclusion criteria (7 listed)
- Pregnancy
- Tuberculosis
- Hepatitis B or C carrier status
- Human immunodeficiency virus-positive status
- Retransplantation or multiorgan transplantation
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 |
|---|---|---|
| EverolimusAlso: CerticanEverolimus: 1 mg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 3-8 ng/mL | Drug | Everolimus |
| Mycophenolate mofetilAlso: CellCeptMycophenolate mofetil: 10-15 mg/kg orally every 12 hours from post-operation day 1 (decrease 50% dose if white blood cell < 4000/mcL) | Drug | Mycophenolate mofetil |
| TacrolimusAlso: PrografTacrolimus: 0.05-0.075 mg/kg orally every 12 hours from post-operation day 1 to achieve trough concentrations of 8-12 ng/mL | Drug | Everolimus, Mycophenolate mofetil |
| MethylprednisoloneAlso: Solu-MedrolMethylprednisolone: 50 mg iv every 6 hours on post-operation day 1, 40 mg iv every 6 hours on post-operation day 2, 30 mg iv every 6 hours on post-operation day 3, 20 mg iv every 6 hours on post-operation day 4, 20 mg iv every 8 hours on post-operation day 5, 20 mg iv every 12 hours on post-operation day 6, 20 mg iv on post-operation day 7 | Drug | Everolimus, Mycophenolate mofetil |
| PrednisoloneAlso: PredoninePrednisolone: 20 mg orally once a day from post-operation day 8 to post-operation week 4, then titrated gradually | Drug | Everolimus, Mycophenolate mofetil |
Primary outcome
Pharmacokinetic profiles
Time frame: Post-operation day 8-10
Pharmacokinetic parameters include the maximum concentration, trough concentration, area under the whole-blood concentration-time curve between 0 and 12 hours, time to maximum concentration, volume of distribution at steady state, and clearance at steady state.
1 secondary outcome
Acute rejection
Time frame: Within the first 2 weeks post-transplantation
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 24 Jul 2019.
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.
Meng-Kun Tsai principal investigator
National Taiwan University Hospital
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 Everolimus, Mycophenolate mofetil and Tacrolimus in people with Drug Interaction Potentiation, run by National Taiwan University Hospital at 1 site in Taiwan.
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 3 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 24 Jul 2019. 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 Taiwan. 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?
Pharmacokinetic profiles (time frame: Post-operation day 8-10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2019.