Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
150
Countries
1
Sites
5
ICD 10: Z94.4 Liver transplant status
To determine whether once-daily formulation of Tacrolimus (Envarsus ®) improves subjective impression of attention and memory performance compared to twice-daily formulation of Tacrolimus
Key facts
- Sponsor
- Universitaetsklinikum Schleswig-Holstein AöR
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Immune system processes [G12]
- Trial duration
- 9 Dec 2020 → 29 Jan 2026
- Decision date (initial)
- 2024-10-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-513963-22-00
- EudraCT number
- 2018-004043-23
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To determine whether once-daily formulation of Tacrolimus (Envarsus ®) improves subjective impression of attention and memory performance compared to twice-daily formulation of Tacrolimus
Conditions and MedDRA coding
ICD 10: Z94.4 Liver transplant status
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Written informed consent
- Age 20 to 75 years
- After 12 months post liver transplantation
- Immunosuppression with a twice daily formulation of Tacrolimus
- Application of the same active Tacrolimus twice daily formulation ≥3 months
- At least mild cognitive impairment
Exclusion criteria 5
- Dialysis treatment during the previous 30 days
- Deafness and/or blindness
- Pregnancy/breastfeeding mothers
- Current participation in another study
- Every other aspect that, in the eye of investigator, makes the patient unable to comply with study procedures
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in subjective impression of QoL concerning attention/concentration and memory between Screening and visit 3 (6 months) using the FEDA (self-report questionnaire on attention and memory)
Secondary endpoints 4
- Cognitive function is assessed using (I) the Trail Making Test – TMT (time criterion), (II) Adaptive Digit Ordering Test – DOT-A (number of correctly sorted digits), (III) Digit Symbol Test – DST (number of correctly sorted items), (IV) Regensburg Stream of Speech Test – RWT (number of correct items), (V) Victoria Stroop Test – VST (time criterion)
- Quality of life (QoL) is measured using the SF36 (summary score). QoL will be performed during Screening, after 6 and after 12 months.
- Everyday executive function is measured by BAFQ (assessment by close relative/partner or care provider). BAFQ will be performed during Screening, after 6 and after 12 months.
- All (serious) adverse events including clinically significant laboratory parameters and relevant liver and kidney functioning parameters are documented at each visit after baseline.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Envarsus 4 mg prolonged-release tablets
PRD1609569 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0.13 mg/kg milligram(s)/kilogram
- Max total dose
- 47.45 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/14/935/007
- MA holder
- CHIESI FARMACEUTICI S.P.A.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Envarsus 0.75 mg prolonged-release tablets
PRD1609514 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0.13 mg/kg milligram(s)/kilogram
- Max total dose
- 47.45 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/14/935/001
- MA holder
- CHIESI FARMACEUTICI S.P.A.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Envarsus 1 mg prolonged-release tablets
PRD1609561 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0.13 mg/kg milligram(s)/kilogram
- Max total dose
- 47.45 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/14/935/004
- MA holder
- CHIESI FARMACEUTICI S.P.A.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 3
PRD344604 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 0.2 mg/kg milligram(s)/kilogram
- Max total dose
- 73 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- 41954.02.00
- MA holder
- ASTELLAS PHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD361965 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 0.20 mg/kg milligram(s)/kilogram
- Max total dose
- 73.00 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- 41954.01.00
- MA holder
- ASTELLAS PHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD335096 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 0.20 mg/kg milligram(s)/kilogram
- Max total dose
- 73.00 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- 41954.00.00
- MA holder
- ASTELLAS PHARMA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaetsklinikum Schleswig-Holstein AöR
- Sponsor organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Address
- Arnold-Heller-Strasse 3, Brunswik Brunswik
- City
- Kiel
- Postcode
- 24105
- Country
- Germany
Scientific contact point
- Organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Contact name
- Felix Braun
Public contact point
- Organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Contact name
- Felix Braun
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 150 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Universitaetsklinikum Schleswig-Holstein AöR
Department of General Surgery, Thoracic-, Visceral-, Transplant- and Pediatric Surgery, Arnold-Heller-Strasse 3, Brunswik, Kiel
Universitaetsklinikum Jena KöR
Department of General, Visceral and Vascular Surgery, Am Klinikum 1, Lobeda, Jena
Charite Universitaetsmedizin Berlin KöR
Department of Surgery, Augustenburger Platz 1, Wedding, Berlin
Universitaetsklinikum Essen AöR
Department of Gastroenterology, Hepatology and Transplant Medicine, Hufelandstrasse 55, Holsterhausen, Essen
Universitaetsklinikum Regensburg AöR
Department of Surgery, Franz-Josef-Strauss-Allee 11, Grass-Oberisling, Regensburg
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 |
|---|---|---|---|---|---|
| Germany | 2020-12-09 | 2026-01-29 | 2020-12-09 | 2025-01-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 5 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | CoFu_Protocol_V1-3_2023-03-14_redacted | 1.3 |
| Recruitment arrangements (for publication) | RecrArr_Blank_for_transition | NA |
| Subject information and informed consent form (for publication) | ICF_V1-1_2020-07-03_redacted | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | 02_2025_Envarsus_075_1_4_Retardtabletten | NA |
| Summary of Product Characteristics (SmPC) (for publication) | 03_FI_Prograf 05 mg 1 mg 5 mg Retardtabletten_Feb-2019 | NA |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-10 | Germany | Acceptable 2024-10-16
|
2024-10-24 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-05-19 | Germany | Acceptable 2024-10-16
|
2025-05-19 |