Clinical trial NCT06057545: Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation
Official title: A Multi-center Interventional Study to Assess Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pediatric Kidney Disease
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 8
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Multi-center, prospective, interventional, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b
Primary purpose: TREATMENT

Brief summary: Recently, a new prolonged-release tablet version of tacrolimus (Envarsus®) using the so-called MeltDose™ (US Patent No. 7,217,431) drug-delivery technology has been approved as immunosuppressive medication for patients after kidney and liver transplantation in adults but not yet in children. Studies in adults proved that Envarsus® provides the same therapeutic effectiveness as the conventional immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile and reduced peak to trough which might result in reduced tacrolimus dosing and subsequently reduced CNI related toxicity. Furthermore, the once daily formulation might result in improved drug adherence.

The aim of this study is to assess pharmacokinetic profiles of Envarsus® as well as effectiveness and tolerability of this drug in children and adolescents ≥ 8 and ≤ 18 years of age.


Eligibility criteria: Inclusion Criteria:

1. caucasian paediatric kidney transplant recipients (single-organ recipients)
2. aged ≥ 8 years but ≤ 18 years who are under tacrolimus (Prograf®) therapy and who are able to swallow tablets with a minimum dose of 0.75 mg / day Envarsus®
3. not less than 6 months after transplantation
4. stable kidney function (delta eGFR \< 10 ml/min/1.73 m2 (CKID formula) over the last 3 months)
5. women of childbearing potential and women without childbearing potential
6. patient/parents/legal guardian(s) must be capable of understanding purpose and risks of the study
7. signed informed consent obtained by patient and parents/legal guardians

Exclusion Criteria:

1. coefficient of variation of tacrolimus trough levels \> 0.35 over the previous 6 months
2. pregnancy/breast feeding
3. instable kidney function
4. hypersensitivity to any of the components of the medications used
5. not eligible for any reason according to the investigator's valuation
6. known positive HIV-1 or HCV test
7. participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)

Primary outcomes:
measure: Full tacrolimus AUC
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacodynamic analysis
timeFrame: 4 weeks
measure: Pharmacogenetic analysis
timeFrame: 4 weeks
measure: Tacrolimus trough levels
timeFrame: 4 weeks
measure: Doses of prolonged-release tacrolimus
timeFrame: 4 weeks
measure: Number of patients with adverse event or toxicity
timeFrame: 10 weeks
measure: Number of adverse events or toxicity per patient
timeFrame: 10 weeks
measure: eGFR (CKiD formula)
timeFrame: 4 weeks
measure: Treatment failure rate
timeFrame: 10 weeks
measure: limited sampling strategy (LSS)
timeFrame: 4 weeks
measure: Taxonomy of the gut microbiome
timeFrame: 10 weeks
measure: Gut microbial metabolism
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: University Hospital Cologne, Pediatrics
city: Essen
country: Germany
facility: University Hospital of Essen, Pediatrics II
city: Hamburg
country: Germany
facility: University Hospital of Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg
Study officials:
affiliation: University Hospital of Essen, Pediatrics II
name: Lars Pape, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: