Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation (Pro-Tac)

University Hospital Essen

Status and phase: Enrolling; Phase 3

Conditions: Pediatric Kidney Disease

Treatments: Drug: Prograf; Drug: Envarsus®

Study type: Interventional

Funder types: Other

Identifiers

NCT06057545

Pro-Tac

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 8 to 18 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Group A - Envarsus followed by Prograf

Experimental group

Description:

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

Treatment:

Drug: Prograf

Drug: Envarsus®

Group B - Prograf followed by Envarsus

Experimental group

Description:

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

Treatment:

Drug: Prograf

Drug: Envarsus®