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

Phase 1

Withdrawn

• Conditions: Kidney Transplant
• Interventions: Drug: Advagraf®; Drug: Generic tacrolimus

• Registration Number: NCT03978494
• Lead Sponsor: Sandoz

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2019-06-05
• Study First Submitted QC: 2019-06-05
• Study First Posted: 2019-06-07
• Status Verified: 2019-09
• Study Start: 2019-09-02
• Last Update Submitted: 2019-09-12
• Last Update Posted: 2019-09-17
• Primary Completion: 2020-05-03
• Study Completion: 2020-05-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Period 1: Advagraf®; Period 2: Generic tacrolimus	Generic tacrolimus	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.
Period 1: Advagraf®; Period 2: Generic tacrolimus	Advagraf®	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.
Period 1: Generic tacrolimus; Period 2: Advagraf®	Advagraf®	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.
Period 1: Generic tacrolimus; Period 2: Advagraf®	Generic tacrolimus	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Sandoz Investigative Site; 🇩🇪 Kiel, Germany