Tacrolimus C:D Ratio Measured in Renal Transplant Recipients Treated With Once-daily Prolonged-release Drugs

NCT06268769 | Recruiting Phase 4

• 2 other identifiers: TaC:Drop2023-503531-18-00
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 9

Brief Summary

The goal of this clinical trial is to compare the bioavailability and practicability of two different formulations of tacrolimus in kidney transplant recipients. The main objective is to demonstrate that Envarsus® (test drug) has superior (higher) oral bioavailability compared with Advagraf™ (comparator drug) at 12 weeks after kidney transplantation. The trial also aims to compare the practicability (handling) of the two drugs using a series of pharmacokinetic parameters and to explore the relationship between drug bioavailability and long-term clinical outcomes, with a special focus on dose-dependent adverse reactions, measured until 3 years post-transplantation. The trial incorporates a pharmacokinetic sub-study designed to profile the peak tacrolimus blood concentration up to 6 hours after drug intake on the day of the 12-week study visit.

Conditions

Immunosuppression

Keywords

Kidney transplantation; Tacrolimus; Concentration/dose ratio

Outcome Measures

Primary Outcomes (1)

• Dose-normalised blood trough level of tacrolimus (concentration/dose ratio)

  To calculate C/D ratio, "concentration" is the blood trough level of tacrolimus measured in a blood sample collected immediately prior to drug dosing on the day of the 12-week trial visit and "dose" is the daily dose taken by the patient on the day prior to the visit. C/D ratio is measured as a surrogate for tacrolimus bioavailability (i.e. systemic exposure per mg of drug). The primary endpoint uses a blood trough level reading that is measured in a central laboratory.

  12 weeks after kidney transplantation

Secondary Outcomes (31)

• Time to reach the first trough level in target range

  Time period measured in days, assessed within the first 2 weeks after kidney transplantation

• Proportion of patients with trough levels lower, within, or higher than the target range

  4 days, 14 days, 28 days and 12 weeks after kidney transplantation

• Mean tacrolimus trough level and inter-patient variability (range) of tacrolimus trough levels

  4 days, 14 days, 28 days and 12 weeks after kidney transplantation

• Mean daily dose of tacrolimus and inter-patient variability (range) of tacrolimus daily dose

  4 days, 14 days, 28 days and 12 weeks after kidney transplantation

• Tacrolimus concentration/dose (C/D) ratio

  4 days, 14 days, 28 days and 1, 2, 3 years after kidney transplantation

Study Arms (2)

Envarsus

EXPERIMENTAL

Participants take prolonged-release tacrolimus tablets (Envarsus) orally once daily and additionally receive standard-of-care immunosuppressive background therapy according to routine practice.

Drug: Tacrolimus Pill

Advagraf

ACTIVE COMPARATOR

Participants take prolonged-release tacrolimus capsules (Advagraf) orally once daily and additionally receive standard-of-care immunosuppressive background therapy according to routine practice.

Drug: Tacrolimus capsule

Interventions

Tacrolimus Pill DRUG

Envarsus tablets dosed to achieve and maintain whole blood trough levels of tacrolimus within a therapeutic range of 5-12 ng/ml during the first 4 weeks post-transplantation, and 5-8 ng/ml thereafter.

Also known as: Envarsus

Envarsus

Tacrolimus capsule DRUG

Advagraf capsules dosed to achieve and maintain whole blood trough levels of tacrolimus within a therapeutic range of 5-12 ng/ml during the first 4 weeks post-transplantation, and 5-8 ng/ml thereafter.

Also known as: Advagraf

Advagraf

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent
• Adult (≥18 years old) male or female
• Renal insufficiency necessitating kidney transplantation and approved to receive a first or second kidney allograft from a living or deceased organ donor
• ABO blood type compatible with the donor kidney
• Able to swallow an oral formulation of tacrolimus in tablet or capsule form

You may not qualify if:

• Multi-organ transplantation
• Any previous solid organ transplantation (other than a first kidney allograft)
• For recipients of a second kidney transplant: loss of first kidney transplant within 2 years after transplantation owing to immunological reasons or recurrence of the underlying renal disease
• Patient and/or donor is positive for HCV, HBV or HIV
• History of any malignancy that could not be curatively treated
• Ongoing abuse of drugs or alcohol
• Signs of advanced liver disease or any signs of liver decompensation
• Ongoing uncontrolled systemic infection
• Severe diarrhoea, vomiting, active peptic ulcer, previous bariatric surgery, or any other gastrointestinal disorder that may affect absorption of tacrolimus
• Planned or foreseeable use of cyclosporine, belatacept or any tacrolimus preparation other than Envarsus® or Advagraf™
• Known contraindication or hypersensitivity to tacrolimus, and/or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics (SmPC) of both Envarsus® and Advagraf™, and/or to any other macrolides
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless using a highly-effective method of contraception
• Participation in another interventional clinical trial in the time period starting from 4 weeks prior to randomisation and throughout the entire trial period
• Any condition or factor which, in the judgement of the investigator, would place the subject at undue risk, invalidate communication with the investigator or study team, or hamper compliance with the trial protocol or follow-up schedule

Sponsors & Collaborators

• Edward Geissler: lead
• Chiesi Pharmaceuticals GmbH: collaborator

Study Sites (9)

University Hospital Aachen, Department of General, Visceral and Transplant Surgery

Aachen, 52074, Germany

NOT YET RECRUITING

Charité Universitätsmedizin, Department of Nephrology and Medical Intensive Care

Berlin, 10117, Germany

NOT YET RECRUITING

University Hospital Dresden, Division of Nephrology

Dresden, 01307, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf, Internal Medicine III (Nephrology, Rheumatology, Endocrinology)

Hamburg, 20251, Germany

RECRUITING

Hannover Medical School, Department of General, Visceral and Transplant Surgery

Hanover, 30625, Germany

RECRUITING

University Hospital Jena, Internal Medicine III, Nephrology

Jena, 07747, Germany

RECRUITING

University Medical Center of the Johannes Gutenberg University Mainz, Medical Clinic I. (Nephrology)

Mainz, 55131, Germany

NOT YET RECRUITING

University Hospital Münster, Medical Clinic D

Münster, 48149, Germany

NOT YET RECRUITING

University Hospital Regensburg, Department of Nephrology

Regensburg, 93053, Germany

RECRUITING

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Bernhard Banas, MD

  University Hospital Regensburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edward K. Geissler, PhD

CONTACT

+49 941 944; edward.geissler@ukr.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Department of Experimental Surgery

Model Details: A dynamic allocation technique assigns participants in a 1:1 ratio to one of two treatment arms: Envarsus tablets (test IMP) or Advagraf capsules (comparator IMP). Randomisation is stratified by two factors: a) trial site, in order to minimise systematic treatment bias at the level of the trial centre and reduce the influence of inter-centre variability, and b) participation in the optional pharmacokinetic sub-study, in order to ensure an equal representation of Envarsus- and Advagraf-treated patients in the sub-study.

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 20, 2024
• Study Start: March 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2029
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)