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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Kidney Transplant
• Intervention / Treatment: Drug: Advagraf®; Drug: Generic tacrolimus

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 Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Grenoble, France
    • Sandoz Investigative Site
  • Limoges, France
    • Sandoz Investigative Site
  • Nantes, France
    • Sandoz Investigative Site
  • Strasbourg, France
    • Sandoz Investigative Site
  • Suresnes, France
    • Sandoz Investigative Site
  • Toulouse, France
    • Sandoz Investigative Site
  • Tours, France
    • Sandoz Investigative Site
• Germany
  • Berlin, Germany
    • Sandoz Investigative Site
  • Bochum, Germany
    • Sandoz Investigative Site
  • Essen, Germany
    • Sandoz Investigative Site
  • Hannover, Germany
    • Sandoz Investigative Site
  • Kaiserslautern, Germany
    • Sandoz Investigative Site
  • Kiel, Germany
    • Sandoz Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Advagraf®; Period 2: 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.	Drug: Advagraf®; Advagraf®1 mg and 5 mg prolonged-release hard capsules once daily (reference medicinal product).; Drug: Generic tacrolimus; Tacrolimus 1 mg and 5 mg prolonged release hard capsules (Sandoz) once daily (test medicinal product)
Experimental: Period 1: Generic tacrolimus; Period 2: 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.	Drug: Advagraf®; Advagraf®1 mg and 5 mg prolonged-release hard capsules once daily (reference medicinal product).; Drug: Generic tacrolimus; Tacrolimus 1 mg and 5 mg prolonged release hard capsules (Sandoz) once daily (test medicinal product)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sandoz

Study record dates

Study Major Dates

• Study Start (Anticipated): September 2, 2019
• Primary Completion (Anticipated): May 3, 2020
• Study Completion (Anticipated): May 3, 2020

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 12, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Kidney transplant; Renal transplant
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 1829-TAC-1; 2018-002672-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No