Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation

NCT06057545 | Unknown Phase 3

• 1 other identifier: Pro-Tac
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

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.

Conditions

Pediatric Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Full tacrolimus AUC

  full tacrolimus AUC calculated from Tac measures before administration of drug and 1.5, 2, 4, 6, 8, 12, 13.5, 14, 16, 20, 24 hours after administration of drug at the time point of 2 weeks (14±7 days) after end of build-up period for each patient under both treatments within two time periods with each a length of 4 weeks

  4 weeks

Secondary Outcomes (11)

• Pharmacodynamic analysis

  4 weeks

• Pharmacogenetic analysis

  4 weeks

• Tacrolimus trough levels

  4 weeks

• Doses of prolonged-release tacrolimus

  4 weeks

• Number of patients with adverse event or toxicity

  10 weeks

Study Arms (2)

Group A - Envarsus followed by Prograf

EXPERIMENTAL

4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf)

Drug: Envarsus®; Drug: Prograf

Group B - Prograf followed by Envarsus

EXPERIMENTAL

4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus)

Drug: Envarsus®; Drug: Prograf

Interventions

Envarsus® DRUG

Treatment sequence: 4 weeks prolonged-release tacrolimus (Envarsus®) once daily

Group A - Envarsus followed by Prograf; Group B - Prograf followed by Envarsus

Prograf DRUG

Treatment sequence: 4 weeks intermediate-release tacrolimus (Prograf®) twice daily

Group A - Envarsus followed by Prograf; Group B - Prograf followed by Envarsus

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• caucasian paediatric kidney transplant recipients (single-organ recipients)
• 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®
• not less than 6 months after transplantation
• stable kidney function (delta eGFR \< 10 ml/min/1.73 m2 (CKID formula) over the last 3 months)
• women of childbearing potential and women without childbearing potential
• patient/parents/legal guardian(s) must be capable of understanding purpose and risks of the study
• signed informed consent obtained by patient and parents/legal guardians

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (4)

University Hospital Cologne, Pediatrics

Cologne, Germany

RECRUITING

University Hospital of Essen, Pediatrics II

Essen, Germany

RECRUITING

University Hospital of Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

University Hospital of Heidelberg

Heidelberg, Germany

RECRUITING

Related Publications (1)

• Karaterzi S, Tonshoff B, Ahlenstiel-Grunow T, Baghai M, Beck B, Buscher A, Eifler L, Giese T, Lezius S, Muller C, Oh J, Zapf A, Weber LT, Pape L. A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial. Front Nephrol. 2024 Feb 20;4:1331510. doi: 10.3389/fneph.2024.1331510. eCollection 2024.

  PMID: 38444519 DERIVED

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Lars Pape, Prof. Dr.

  University Hospital of Essen, Pediatrics II

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Grimm

CONTACT

+4920172377414; julia.grimm@uk-essen.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, prospective, interventional, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: September 28, 2023
• Study Start: April 25, 2023
• Primary Completion: December 1, 2024
• Study Completion: March 1, 2025
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

DE (4)