Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
26
Countries
1
Sites
1
Kidney transplantation
To investigate the effect of calcium supplement treatment on tacrolimus and mycophenolate mofetil pharmacokinetics when administered together in stable kidney transplant recipients.
Key facts
- Sponsor
- Oslo University Hospital HF
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]
- Trial duration
- 25 Sep 2024 → 4 Dec 2025
- Decision date (initial)
- 2024-09-25
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Oslo University Hospital
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic
To investigate the effect of calcium supplement treatment on tacrolimus and mycophenolate mofetil pharmacokinetics when administered together in stable kidney transplant recipients.
Secondary objectives 4
- Investigate the effect of calcium supplement on absolute bioavailability of tacrolimus and mycophenolate mofetil
- Compare limited sampling predicted Tac and MPA AUC0-12 between venous and capillary microsamples
- To investigate associations between gut microbiota and Tac, MPA and prednisolone pharmacokinetics
- Update current population pharmacokinetic model by including absolute bioavailability and prednisolone exposure
Conditions and MedDRA coding
Kidney transplantation
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10023438 | Kidney transplant | 10042613 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Kidney transplant recipients on stable immunosuppressive therapy for the last 5 days
- Immunosuppressive drug regimen containing Prograf® (tacrolimus twice daily), CellCept® (mycophenolate mofetil twice daily) and prednisolone.
- Above 18 years of age
- Clinical in need of calcium/vitamin D supplement, defined as a dietary calcium intake <1000 mg/day.
- Able to comply with the medical treatment on their own.
- Signed informed consent.
Exclusion criteria 9
- Recent (1 week) rejection episode of the kidney graft treated with methylprednisolone.
- Ongoing acute infectious disease, including any eventual treatment for the infection, that may influence drug pharmacokinetics
- Concomitant treatment with interacting drugs such as (but not limited to): diltiazem, verapamil, fenytoin, carbamazapin, fluconazole, ketoconazole, vorikonazole, erythromycin, clarithromycin, ritonavir.
- Concomitant anti-coagulation treatment that affects capillary finger-prick sampling.
- Severe diarrhoea.
- Women who are breastfeeding, pregnant patients or women of childbearing potential (WOCBP) not on highly effective contraception (not acceptable methods: progesterone-only oral hormonal contraception, male/female condom without spermicide or cap, diaphragm or sponge with spermicide
- Hypercalcemia or hypercalciuria
- Nephrolithiasis
- Hypervitaminosis D
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- AUC0-12 and Cmax of tacrolimus/mycophenolate with:without (calcium supplement coadministration) ratio (according to EMA bioequivalence guidelines)
Secondary endpoints 5
- Tacrolimus pharmacokinetic parameters and variables such as AUC0-12, Cmax, Fabs, C0, C12, CL, popPK model parameters
- Mycophenolate mofetil pharmacokinetic parameters and variables such as AUC0-12, Cmax, Fabs, C0, C12, CL, popPK model parameters
- Prednisolone pharmacokinetic parameters and variables such as AUC0-12, Cmax, Fabs, C0, C12, CL, popPK model parameters
- Metagenomic feces analyses
- feces derived ex vivo drug conversion rates
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
PRD10226711 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL AND IV
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 560 mg milligram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- 8912/2016/02
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- Romania
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
CellCept 500 mg film-coated tablets
PRD2153968 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL AND IV
- Max daily dose
- 2 g gram(s)
- Max total dose
- 28 g gram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- EU/1/96/005/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Calcigran Forte 500 mg/400 IE tyggetabletter
PRD9221275 · Product
- Active substance
- Colecalciferol
- Pharmaceutical form
- CHEWABLE TABLET
- Route of administration
- ORAL
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 7 g gram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- A12AX — CALCIUM, COMBINATIONS WITH OTHER DRUGS
- Marketing authorisation
- 97-1657
- MA holder
- ORIFARM HEALTHCARE A/S
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD3161796 · Product
- Active substance
- Prednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 280 mg milligram(s)
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- PL 17907/0456
- MA holder
- BRISTOL LABORATORIES LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Oslo University Hospital HF
- Sponsor organisation
- Oslo University Hospital HF
- Address
- Taarnbygget, Kirkeveien 166 Kirkeveien 166
- City
- Oslo
- Postcode
- 0450
- Country
- Norway
Scientific contact point
- Organisation
- Oslo University Hospital HF
- Contact name
- Anders Åsberg
Public contact point
- Organisation
- Oslo University Hospital HF
- Contact name
- Anders Åsberg
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ended | 26 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Norway | 2024-09-25 | 2025-12-04 | 2024-09-25 | 2025-11-26 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-515164-30-00 | 3 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangments | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC CalcigranForte | 0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC CellCept | 0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Prednisolon | 0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Prograf | 0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Prograf_IV | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NO 2024-515164-30-00 | 3 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-24 | Norway | Acceptable 2024-09-20
|
2024-09-25 |