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Trial record 1 of 1 for:    pro-tac | Germany
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Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation (Pro-Tac)

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ClinicalTrials.gov Identifier: NCT06057545
Recruitment Status : Recruiting
First Posted : September 28, 2023
Last Update Posted : September 28, 2023
Sponsor:
Information provided by (Responsible Party):
University Hospital, Essen

Study Description
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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.


Condition or disease Intervention/treatment Phase
Pediatric Kidney Disease Drug: Envarsus® Drug: Prograf Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Multi-center, prospective, interventional, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center Interventional Study to Assess Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation
Actual Study Start Date : April 25, 2023
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arms and Interventions
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Arm Intervention/treatment
Experimental: Group A - Envarsus followed by Prograf
4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf)
 Drug: Envarsus®
Treatment sequence: 4 weeks prolonged-release tacrolimus (Envarsus®) once daily

Drug: Prograf
Treatment sequence: 4 weeks intermediate-release tacrolimus (Prograf®) twice daily
Experimental: Group B - Prograf followed by Envarsus
4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus)
 Drug: Envarsus®
Treatment sequence: 4 weeks prolonged-release tacrolimus (Envarsus®) once daily

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


Outcome Measures
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Primary Outcome Measures :
  1. Full tacrolimus AUC [ Time Frame: 4 weeks ]
    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


Secondary Outcome Measures :
  1. Pharmacodynamic analysis [ Time Frame: 4 weeks ]
    Assessment of efficacy in terms of residual expression of NFAT regulated genes, expressed as % of expression at C0 (time point before drug administration set at 100%) at 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

  2. Pharmacogenetic analysis [ Time Frame: 4 weeks ]
    Number of patients with SNPs in selected genes (CYP3A4, CYP3A5, ABCD1)

  3. Tacrolimus trough levels [ Time Frame: 4 weeks ]
    Tacrolimus trough levels in ng/mL, compared intra- and interindividually.

  4. Doses of prolonged-release tacrolimus [ Time Frame: 4 weeks ]
    Doses of prolonged-release tacrolimus (Envarsus®) in ng/mL.

  5. Number of patients with adverse event or toxicity [ Time Frame: 10 weeks ]
    Cumulative dosage and signs of tacrolimus toxicity and adverse events. Potentially tacrolimus associated adverse events and toxicity are recorded individually and compared with individual tacrolimus AUCs. Special attention is taken e.g. towards metabolic (elevated concentration of blood glucose, fat), hematopoetic (cell counts), neurological (tremor, headache), renal (change in glomerular filtration rate), gastrointestinal (diarrhea, nausea), hepatic (cholestasis, elevated transaminases, blood clotting disorder), elevated blood pressure.

  6. Number of adverse events or toxicity per patient [ Time Frame: 10 weeks ]
    Special attention is taken e.g. towards metabolic (elevated concentration of blood glucose, fat), hematopoetic (cell counts), neurological (tremor, headache), renal (change in glomerular filtration rate), gastrointestinal (diarrhea, nausea), hepatic (cholestasis, elevated transaminases, blood clotting disorder), elevated blood pressure.

  7. eGFR (CKiD formula) [ Time Frame: 4 weeks ]
    eGFR (CKiD formula) comparing the two study phases

  8. Treatment failure rate [ Time Frame: 10 weeks ]
    composite endpoint: any patient who experienced death, graft failure, BPAR or lost to follow-up

  9. limited sampling strategy (LSS) [ Time Frame: 4 weeks ]
    LSS driven 24h-AUC estimation

  10. Taxonomy of the gut microbiome [ Time Frame: 10 weeks ]
    Taxonomy of the gut microbiome using metagenomic sequencing

  11. Gut microbial metabolism [ Time Frame: 10 weeks ]
    Functional assessment of the gut microbiome using LC-MS based metabolomics


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06057545


Contacts
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Contact: Julia Grimm +4920172377414 julia.grimm@uk-essen.de

Locations
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Germany
University Hospital Cologne, Pediatrics Recruiting
Cologne, Germany
Contact: Lutz Weber, Prof. Dr.         
University Hospital of Essen, Pediatrics II Recruiting
Essen, Germany
Contact: Lars Pape, Prof. Dr.         
University Hospital of Hamburg-Eppendorf Recruiting
Hamburg, Germany
Contact: Jun Oh, Prof. Dr.         
University Hospital of Heidelberg Recruiting
Heidelberg, Germany
Contact: Burkhard Tönshoff, Prof. Dr.         
Sponsors and Collaborators
University Hospital, Essen
Investigators
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Principal Investigator: Lars Pape, Prof. Dr. University Hospital of Essen, Pediatrics II
More Information
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Responsible Party: University Hospital, Essen
ClinicalTrials.gov Identifier: NCT06057545    
Other Study ID Numbers: Pro-Tac
First Posted: September 28, 2023    Key Record Dates
Last Update Posted: September 28, 2023
Last Verified: September 2023

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Tacrolimus
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action