TransplantationPhase 4IMPAKTNCT03076151
Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
A Phase 4 study testing Tacrolimus monohydrate (ADOPORT®) in people with Transplantation and Kidney, run by University Hospital, Limoges at 5 sites in France.
Trial summary
Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transplantation, Kidney, Pharmacokinetic
- What is being tested?
- Tacrolimus monohydrate (ADOPORT®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesFrance
- Study dates
- 12 Feb 2018to 31 Jul 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject's written informed consent of the study
- Male and female (>= 18 years)
- Recipients of a first kidney allograft
- Patients transplanted for less than 7 days at enrolment
- Patients affiliated to a social security system
Who cannot join
- Patients presenting any contraindication to tacrolimus according to the summary of product characteristics of Adoport®
- Patient presenting anti-HLA antibodies against the graft in pre-transplantation (DSA)
- Recipients of any transplanted organ other than the kidney
- Pregnant (positive BHCG test) or lactating women
- Women without any method of contraception, except for women with no childbearing potential (according to the guidelines of the working group, Clinical Trial Facilitation Group, related to contraception and pregnancy test in clinical trials)
- Patients participating in any other interventional clinical study at inclusion as well as during the whole course of the current study
- Patient under judicial protection
- Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Amiens Picardie University Hospital
Amiens, 80054
Limoges University Hospital
Limoges, 87042
Poitiers University Hospital
Poitiers, 86000
CHU de ROUEN
Rouen, 76013
Tours University Hospital
Tours, 37000
About this study
Official title: Interventional Multicentre Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Adoport® is an immediate-release formulation of tacrolimus, to be administered twice daily. Because of a narrow therapeutic window and a better correlation between pre-dose level and effects than between dose and effect, therapeutic drug monitoring (TDM) based on trough whole blood tacrolimus concentrations is recommended for Adoport®. TDM helps to minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).
As reported in a consensus document from a consortium of European experts on tacrolimus TDM, the interdose area-under-the curve (AUC0-12h) is expected to be the best marker of tacrolimus exposure. However, tacrolimus monitoring based on full AUC0-12h is difficult to set up in routine, due to clinical constraints and the necessity of multiple samples. Calculation of the AUC0-12h using Bayesian estimation and a limited sampling strategy, i.e. a few blood samples collected during the early phase post-dose would represent an elegant solution, as already done for other tacrolimus formulations.
Furthermore, the pharmacokinetics (PK) of tacrolimus is influenced by a single nucleotide polymorphism within intron 3 of cytochrome P450 3A5 (CYP3A5). Patients who carry at least one CYP3A5*1 allele are considered to be CYP3A5 expressors (about 12% of the Caucasian population, Hapmap project) and thus require a 1.5 to 2-fold higher starting dose than CYP3A5*3/*3 carriers to reach the predefined target exposure early after transplantation. Although this polymorphism showed no impact on the performance of the Bayesian estimators previously developed for other tacrolimus formulation, the patient status for CYP3A5*3 will be considered in this pharmacokinetic study as a potential covariate in, or confounding factor of, the PK model. Specifically, owing to a 12% frequency in the White European population, about 4 patients carriers of the CYP3A5*1 allele are expected in this study; the performance of the PK model and Bayesian estimator developed will be specifically evaluated in this subgroup.
- Conditions
- Transplantation, Kidney, Pharmacokinetic
- Being tested
- Tacrolimus monohydrate (ADOPORT®)
- Keywords
- Transplantation, Kidney, pharmacokinetic, bayesian estimators
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus monohydrate (ADOPORT®)Drug
Pharmacokinetic of Tracrolimus (ADOPORT®) on 9 blood sampling by kinetics on 4 kinetics
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus monohydrate (ADOPORT®) | Experimental | patients with de novo Kidney Transplantation under Tacrolimus (ADOPORT®) treatment. Receives: Drug: Tacrolimus monohydrate (ADOPORT®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tacrolimus bayesian estimator performance
The evaluation of Bayesian estimator performance will be based on its capacity to predict tacrolimus AUC (Area Under the Curve), expressed as the bias (%) between the predicted AUC with the PK model and the tacrolimus AUC calculated using the linear trapezoidal rule.
Measured: Month 3
Secondary outcomes (1)
Tacrolimus concentrations predicted by the PK model using a limited sample strategy
The evaluation of the Bayesian estimator performance will be based on its capacity to predict, using a limited number of samples collected during the early phase post-dose, observed tacrolimus AUC0-12h measured using the non-compartmental trapezoidal method with all the time points
Measured: Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2017
- Study start12 Feb 2018
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre Marquet, MD, Principal investigator, University Hospital, Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03076151
- Sponsor's protocol ID
- I16009 (IMPAKT)
- Acronym
- IMPAKT
- Status last verified
- Jul 2025
- First submitted
- 2 Feb 2017
- Last updated
- 20 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Marquet P, Destere A, Monchaud C, Rerolle JP, Buchler M, Mazouz H, Etienne I, Thierry A, Picard N, Woillard JB, Debord J. Clinical Pharmacokinetics and Bayesian Estimators for the Individual Dose Adjustment of a Generic Formulation of Tacrolimus in Adult Kidney Transplant Recipients. Clin Pharmacokinet. 2021 May;60(5):611-622. doi: 10.1007/s40262-020-00959-y. Epub 2020 Nov 24.
PubMed 33230714
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interventional Multicentre Pharmacokinetic Study of Adoport® (Tacrolimus) in Patients With de Novo Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03076151
- Acronym / sponsor ID
- IMPAKT / I16009 (IMPAKT)
- Conditions
- Transplantation, Kidney, Pharmacokinetic
- Keywords
- Transplantation, Kidney, pharmacokinetic, bayesian estimators
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- 12 Feb 2018 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 10 Mar 2017 (actual)
- 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.
Tacrolimus is a calcineurin inhibitor widely used for the prevention of allograft rejection in solid organ and bone marrow transplantation. It is characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Adoport® is an immediate-release formulation of tacrolimus, to be administered twice daily. Because of a narrow therapeutic window and a better correlation between pre-dose level and effects than between dose and effect, therapeutic drug monitoring (TDM) based on trough whole blood tacrolimus concentrations is recommended for Adoport®. TDM helps to minimize the risk of acute rejection and the occurrence of adverse effects (mainly nephrotoxicity and, to a lesser extent, neurotoxicity).
As reported in a consensus document from a consortium of European experts on tacrolimus TDM, the interdose area-under-the curve (AUC0-12h) is expected to be the best marker of tacrolimus exposure. However, tacrolimus monitoring based on full AUC0-12h is difficult to set up in routine, due to clinical constraints and the necessity of multiple samples. Calculation of the AUC0-12h using Bayesian estimation and a limited sampling strategy, i.e. a few blood samples collected during the early phase post-dose would represent an elegant solution, as already done for other tacrolimus formulations.
Furthermore, the pharmacokinetics (PK) of tacrolimus is influenced by a single nucleotide polymorphism within intron 3 of cytochrome P450 3A5 (CYP3A5). Patients who carry at least one CYP3A5*1 allele are considered to be CYP3A5 expressors (about 12% of the Caucasian population, Hapmap project) and thus require a 1.5 to 2-fold higher starting dose than CYP3A5*3/*3 carriers to reach the predefined target exposure early after transplantation. Although this polymorphism showed no impact on the performance of the Bayesian estimators previously developed for other tacrolimus formulation, the patient status for CYP3A5*3 will be considered in this pharmacokinetic study as a potential covariate in, or confounding factor of, the PK model. Specifically, owing to a 12% frequency in the White European population, about 4 patients carriers of the CYP3A5*1 allele are expected in this study; the performance of the PK model and Bayesian estimator developed will be specifically evaluated in this subgroup.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus monohydrate (ADOPORT®) | Experimental | Drug: Tacrolimus monohydrate (ADOPORT®)patients with de novo Kidney Transplantation under Tacrolimus (ADOPORT®) treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject's written informed consent of the study
- Male and female (>= 18 years)
- Recipients of a first kidney allograft
- Patients transplanted for less than 7 days at enrolment
- Patients affiliated to a social security system
Key exclusion criteria (8 listed)
- Patients presenting any contraindication to tacrolimus according to the summary of product characteristics of Adoport®
- Patient presenting anti-HLA antibodies against the graft in pre-transplantation (DSA)
- Recipients of any transplanted organ other than the kidney
- Pregnant (positive BHCG test) or lactating women
- Women without any method of contraception, except for women with no childbearing potential (according to the guidelines of the working group, Clinical Trial Facilitation Group, related to contraception and pregnancy test in clinical trials)
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 |
|---|---|---|
| Tacrolimus monohydrate (ADOPORT®)Pharmacokinetic of Tracrolimus (ADOPORT®) on 9 blood sampling by kinetics on 4 kinetics | Drug | Tacrolimus monohydrate (ADOPORT®) |
Primary outcome
Tacrolimus bayesian estimator performance
Time frame: Month 3
The evaluation of Bayesian estimator performance will be based on its capacity to predict tacrolimus AUC (Area Under the Curve), expressed as the bias (%) between the predicted AUC with the PK model and the tacrolimus AUC calculated using the linear trapezoidal rule.
1 secondary outcome
Tacrolimus concentrations predicted by the PK model using a limited sample strategy
Time frame: Month 3
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 20 Jul 2025.
- Results publication: PubMed 33230714Marquet P, Destere A, Monchaud C, Rerolle JP, Buchler M, Mazouz H, Etienne I, Thierry A, Picard N, Woillard JB, Debord J. Clinical Pharmacokinetics and Bayesian Estimators for the Individual Dose Adjustment of a Generic Formulation of Tacrolimus in Adult Kidney Transplant Recipients. Clin Pharmacokinet. 2021 May;60(5):611-622. doi: 10.1007/s40262-020-00959-y. Epub 2020 Nov 24.
- Individual participant dataSharing planned: No
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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.
Pierre Marquet, MD principal investigator
University Hospital, Limoges
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus monohydrate (ADOPORT®) in people with Transplantation and Kidney, run by University Hospital, Limoges at 5 sites in France.
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 8 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 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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?
Tacrolimus bayesian estimator performance (time frame: Month 3). 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 NCT03076151, which also lists 1 linked publication.
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 20 Jul 2025.