Study to Compare Pharmacokinetics of Tacrolimus Prolonged-release (PR) Capsules and Advagraf® PR Capsules in Stable Kidney Transplant Patients.

Study Overview
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Brief Summary
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Study to compare pharmacokinetics of tacrolimus prolonged-release (PR) capsules and Advagraf® PR capsules in stable kidney transplant patients.

Detailed Description
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Initially, patients will enter a short screening period, and those who continue to meet the inclusion and exclusion criteria will be randomized to receive either test or reference medicinal product in Period 1. In period 2 they will switch to the other formulation. During the whole treatment period four full-pharmacokinetics profiles will be established.

Official Title
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Randomized, Multicenter, Open-Label, Two-period, Two-sequence Crossover Comparative Pharmacokinetic Study of Generic Tacrolimus (Sandoz) and Advagraf® in Stable Renal Transplant Patients (TODAY)

Conditions
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Kidney Transplant

Intervention / Treatment
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* Drug: Advagraf®
* Drug: Generic tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥18 years; Patients with a Body Mass Index (BMI) included in the interval [18.5-33.0] kg/m²; Patients who received a primary kidney transplant at least 12 months prior to study entry Exclusion Criteria: Evidence or suspicion of ongoing or persistent, acute or chronic rejection; Requirement for dialysis within the six months prior to study entry; Glomerular filtration rate (GFR) <30 mL/min Pregnant or breastfeeding women, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test; Intolerance to tacrolimus, excipients (including lactose, fructose or galactose), or similar products;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: Advagraf®; Period 2: Generic tacrolimus<br>In Period 1 patients will receive branded tacrolimus (Advagraf®) orally once-a-day and in Period 2 patients will receive the generic tacrolimus (Sandoz) orally once-a-day. | Drug: Advagraf®<br>* Advagraf®1 mg and 5 mg prolonged-release hard capsules once daily (reference medicinal product).<br>Drug: Generic tacrolimus<br>* Tacrolimus 1 mg and 5 mg prolonged release hard capsules (Sandoz) once daily (test medicinal product)<br>|
| Experimental: Period 1: Generic tacrolimus; Period 2: Advagraf®<br>In Period 1 patients will receive the generic tacrolimus (Sandoz) orally once-a-day and in Period 2 patients will receive branded tacrolimus (Advagraf®) orally once-a-day. | Drug: Advagraf®<br>* Advagraf®1 mg and 5 mg prolonged-release hard capsules once daily (reference medicinal product).<br>Drug: Generic tacrolimus<br>* Tacrolimus 1 mg and 5 mg prolonged release hard capsules (Sandoz) once daily (test medicinal product)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-τ)ss | Area under the whole blood concentration curve during a dosage interval (τ=24 hours) at steady state | Day 21 of each treatment period | 
| Cmax,ss | Maximum whole blood concentration at steady state | Day 21 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-τ)ss | Area under the whole blood concentration curve during a dosage interval (τ=24 hours) at steady state | Day 14 of each treatment period | 
| Cmax,ss | Maximum whole blood concentration at steady state | Day 14 of each treatment period | 
| Cmin,ss | Minimum whole blood concentration at steady state | Days 14 and 21 of each treatment period | 
| Cτ,ss | Concentration at the end of the dosing interval at steady state | Days 14 and 21 of each treatment period | 
| Cav | Average concentration during a dosing interval: AUC(0-τ)/τ | Days 14 and 21 of each treatment period | 
| Tmax,ss | Time to reach maximum (peak) plasma concentration at steady state | Days 14 and 21 of each treatment period | 
| AUC(0-τ)ss coefficient of variation | Intra-patient pharmacokinetics variability evaluated by calculating AUC(0-τ)ss coefficient of variation | Days 14 and 21 of each treatment period | 
| Cmax,ss coefficient of variation | Intra-patient pharmacokinetics variability evaluated by calculating Cmax,ss coefficient of variation | Days 14 and 21 of each treatment period | 
| % Fluctuation | Degree of fluctuation of the analyte concentration levels over one dosing interval: 100*(Cmax,ss - Cmin,ss)/Cav. | Days 14 and 21 of each treatment period | 
| %Swing | Degree of change of the analyte concentration levels over one dosing interval: 100*(Cmax,ss - Cτ,ss)/Cτ,ss. | Days 14 and 21 of each treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant; Renal transplant