Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients

Study Overview
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Brief Summary
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Repeated 12-hour pharmacokinetic (PK) investigations in renal transplant recipients for parallel sampling of standard venous bloods samples and finger prick micro samples (Mitra tips). Primary aim to validate the micro sampling tacrolimus concentrations against venous blood concentrations.

Detailed Description
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Renal transplant recipients using Prograf® as part of their immunosuppressive regimen will be included in the study. Patients will receive oral and written study information and sign the informed consent before entering the study. A 12-hour pharmacokinetic investigation will be performed when Tac doses have been stable for at least 7 days (approximately 3-4 weeks posttransplant). They will continue on unchanged doses of tacrolimus as before PK investigation 1 (PK1). After at least another 7 days a second 12h PK-investigation (PK2) will be performed. If Tac doses needs to be changed after PK1 and before PK2 the second PK will not be performed. Tac doses and blood concentration obtained as part of standard follow-up of the patients will be included in a non-parametric population model to obtain individually optimal sampling times for each patient using the MMopt function in Pmetrics®. During both PK1 and PK2 the patients themselves will be instructed to take two home sampling micro samples (Mitra® microsampling device) just prior to the standard vacutainer samples are obtained. Both the micro- and vacutainer samples will be drawn in 2 parallel samples right after each other and one will be mailed to the laboratory via standard mail. During PK1 the sampling times will be the same and standardized for all patients; before (0h) and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours after dose administration. During PK2 individually optimized sampling times based on 2, 3 and 4 samples will be determined using the MMopt function in Pmetrics and utilizing all individual dose and concentration information from before PK2, including the rich sampling during PK1. Spread over the entire study period, at least 6 real life home samplings for trough (C0) of Tac will also be performed by the patient and mailed to the hospital. Tacrolimus induced tremor will be measured with a center-developed method utilizing infrared determined positioning (sampling ever 5 ms) of hand joints in the x-, y, z axis.

Official Title
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Dose Adjustment of Tacrolimus Based on Home Sampling in Renal Transplant Recipients

Conditions
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Renal Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Micro sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant recipients Females and males Patients receiving tacrolimus as part of their immunosuppressive therapy (clinical decision not influenced by this study) Exclusion Criteria: Patients on concomitant drugs with known pharmacokinetic interaction with tacrolimus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Only one arm in the present study | Diagnostic Test: Micro sampling<br>* Compare finger prick micro samples with venous blood samples for measuring whole blood tacrolimus concentrations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute bias of micro sample tacrolimus concentrations | absolute bias (mico- minus vacutainer sampling) over the clinical range (1 to 40 µg/L) of micro sampled, including simulated home sampled, Tac trough concentrations | Within one dose interval of 12 hours | 
| Relative bias of micro sample tacrolimus concentrations | Relative bias (mico- minus vacutainer sampling divided by vacutainer sampled) over the clinical range (1 to 40 µg/L) of micro sampled, including simulated home sampled, Tac trough concentrations | Within one dose interval of 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| popPK Bayesian predicted tacrolimus trough concentration | Absolute and relative predictive error of population pharmacokinetic Bayesian estimated Tac trough concentration based on LSS with 2, 3 and 4 individually optimal sampling times more than 2 hours from trough | Within one dose interval of 12 hours | 
| PK Bayesian predicted tacrolimus AUC0-12 | Absolute and relative predictive error of population pharmacokinetic Bayesian estimated Tac AUC0-12 based on LSS with 2, 3 and 4 individually optimal sampling times | Within one dose interval of 12 hours | 
| Tacrolimus tremor PK/PD relation | Description of the mathematical relation between measured tacrolimus blood concentrations and specific Tac tremor over a dose interval | Within one dose interval of 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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analytical method validation, renal transplantation, limited sampling strategy