Overview
Sponsor-declared trial summary
kidney failure werefor need for kidney transplant
The objective is to evaluate if the LCPT dose can be reduced in comparison with tacrolimus-ER and still achieve similar tacrolimus levels in the therapeutic range in patients who receive tacrolimus who need a relatively high dose of tacrolimus, a C/D ratio < 1.05
Key facts
- Sponsor
- Stichting Amsterdam UMC
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08]
- Trial duration
- completed 28 Jan 2025
- Decision date (initial)
- 2025-01-17
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-515542-16-03
- EudraCT number
- 2020-001101-22
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The objective is to evaluate if the LCPT dose can be reduced in comparison with tacrolimus-ER and still achieve similar tacrolimus levels in the therapeutic range in patients who receive tacrolimus who need a relatively high dose of tacrolimus, a C/D ratio < 1.05
Conditions and MedDRA coding
kidney failure werefor need for kidney transplant
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-515542-16-02 | Personalized Use of Resources Study (PURE) | Stichting Amsterdam UMC |
| 2024-515542-16-01 | Personalized Use of Resources Study (PURE) | Stichting Amsterdam UMC |
| 2024-515542-16-00 | Personalized Use of Resources Study (PURE) | Stichting Amsterdam UMC |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Patients aged 18 to 70 years, inclusive, with a stable renal function; b. Patients who are at least 6 months until five years after first transplantation, who are not immunized (PRA<5%), with therapeutic tacrolimus concentrations between 4-9 ng/L, who are on a stable tacrolimus dose (same dosage of Tacrolimus extended release for the last month), with a C/D ratio < 1.05 ng/mL×1/mg; c. Patients must provide written informed consent; and d. Patients of childbearing potential must agree to use highly effective methods of contraception during the study.
Exclusion criteria 1
- a. Patient received or is receiving treatment for acute rejection prior to initiation of study; b. Donor Specific antibody positivity and patients who are immunized (PRA≥5%); c. Chronic diarrhoea; d. Use of phenytoin, carbamazepine, phenobarbital, primidone, rifampin, caspofungin, erythromycin, clarithromycin, fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole, fluoxetine, fluvoxamine, sertraline, venlafaxine, mirtazapine, paroxetine, diltiazem, verapamil, or amiodarone; e. Thyroid dysfunction; f. Excessive use of caffeine (more than use of 5 IE daily); g. Excessive use of alcohol (more than 2 IE daily); or h. Patients who are pregnant.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The objective is to evaluate if the LCPT dose can be reduced in comparison with tacrolimus-ER and still achieve similar tacrolimus levels in the therapeutic range in patients who have a C/D ratio < 1.05 ng/mL×1/mg.
Secondary endpoints 1
- To evaluate if the switch design of the study leads to a lower pill burden; - to evaluate if the LCPT switch leads to less side effects; - to evaluate if the LCPT switch leads to less variability in trough levels; - to evaluate if patients with CYP3A5*1 allele is a factor to consider when prescribing tacrolimus variants; and - to evaluate differences in Cmax, Tmax and 24hour AUC levels.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Envarsus 4 mg prolonged-release tablets
PRD11085941 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 10000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- PLGB 08829/0185
- MA holder
- CHIESI LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Envarsus 1 mg prolonged-release tablets
PRD11085940 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 1000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- PLGB 08829/0184
- MA holder
- CHIESI LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Envarsus 0.75 mg prolonged-release tablets
PRD11085939 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 1000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- PLGB 08829/0183
- MA holder
- CHIESI LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 3
Advagraf 5 mg prolonged-release hard capsules
PRD324666 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 10000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/07/387/026
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Advagraf 0.5 mg prolonged-release hard capsules
PRD324600 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 30 mg milligram(s)
- Max treatment duration
- 10000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/07/387/002
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Advagraf 1 mg prolonged-release hard capsules
PRD324615 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 10000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/07/387/005
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Stichting Amsterdam UMC
- Sponsor organisation
- Stichting Amsterdam UMC
- Address
- De Boelelaan 1117
- City
- Amsterdam
- Postcode
- 1081 HV
- Country
- Netherlands
Scientific contact point
- Organisation
- Stichting Amsterdam UMC
- Contact name
- drs Nienke Manson
Public contact point
- Organisation
- Stichting Amsterdam UMC
- Contact name
- drs Nienke Manson
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 25 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_protocol EU CT 2024-515542-16-03 | 5.1 |
| Recruitment arrangements (for publication) | Replacement document | 1 |
| Subject information and informed consent form (for publication) | SIS and ICF adult PURE | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Advagraf | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Envarsus | 1 |
| Synopsis of the protocol (for publication) | Replacement document | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-03 | Netherlands | Acceptable 2025-01-17
|
2025-01-17 |