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

• Sponsor: Sandoz (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT03978494
• Collaborator: (none)
• Enrollment: 0
• Locations: 13
• Arms: 2
• Anticipated Duration (Months): 8
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant	Drug: Advagraf®; Drug: Generic tacrolimus	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Randomized, Multicenter, Open-Label, Two-period, Two-sequence Crossover Comparative Pharmacokinetic Study of Generic Tacrolimus (Sandoz) and Advagraf® in Stable Renal Transplant Patients (TODAY)
• Anticipated Study Start Date: Sep 2, 2019
• Anticipated Primary Completion Date: May 3, 2020
• Anticipated Study Completion Date: May 3, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

1. 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

2. Cmax,ss [Day 21 of each treatment period]

   Maximum whole blood concentration at steady state

Secondary Outcome Measures

1. 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

2. Cmax,ss [Day 14 of each treatment period]

   Maximum whole blood concentration at steady state

3. Cmin,ss [Days 14 and 21 of each treatment period]

   Minimum whole blood concentration at steady state

4. Cτ,ss [Days 14 and 21 of each treatment period]

   Concentration at the end of the dosing interval at steady state

5. Cav [Days 14 and 21 of each treatment period]

   Average concentration during a dosing interval: AUC(0-τ)/τ

6. Tmax,ss [Days 14 and 21 of each treatment period]

   Time to reach maximum (peak) plasma concentration at steady state

7. 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

8. 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

9. % 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.

10. %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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sandoz Investigative Site	Grenoble		France
2	Sandoz Investigative Site	Limoges		France
3	Sandoz Investigative Site	Nantes		France
4	Sandoz Investigative Site	Strasbourg		France
5	Sandoz Investigative Site	Suresnes		France
6	Sandoz Investigative Site	Toulouse		France
7	Sandoz Investigative Site	Tours		France
8	Sandoz Investigative Site	Berlin		Germany
9	Sandoz Investigative Site	Bochum		Germany
10	Sandoz Investigative Site	Essen		Germany
11	Sandoz Investigative Site	Hannover		Germany
12	Sandoz Investigative Site	Kaiserslautern		Germany
13	Sandoz Investigative Site	Kiel		Germany

Sponsors and Collaborators

• Sandoz

Investigators

• Study Director: Sandoz, Sandoz

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT03978494
• Other Study ID Numbers: 1829-TAC-1; 2018-002672-40
• First Posted: Jun 7, 2019
• Last Update Posted: Sep 17, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sandoz: Kidney transplant; Renal transplant
• Additional relevant MeSH terms: Tacrolimus

Study Results

No Results Posted as of Sep 17, 2019