PK Study in Diabetic Transplant récipients : From Twice-daily Tacrolimus to Once-daily Extended-release Tacrolimus (SPK-PK)

Comparison of Pharmacokinetic (PK) Levels Before and After Conversion From Twice-daily Tacrolimus to Once-daily Extended-release Tacrolimus (LCPT) in Diabetic Transplant récipients

The investigators believe that the pharmacological properties of Envarsus®, well studied in kidney transplantation, may be also suitable after simultaneous kidney and pancreas transplantation than Prograf. Indeed, Envarsus® has demonstrated a clinical efficacy and safety in a complete clinical development plan.

This study is to establish the pharmacokinetic profile of tacrolimus prolonged-release (hereafter referred to as 'ENVARSUS®') in diabetics who have undergone kidney and pancreas transplantation, and compare it to the pharmacokinetic profile of standard twice-daily tacrolimus. The study will be conducted in 25 patients hospitalized at Nantes University Hospital.

Study Overview

• Status: Completed
• Conditions: Diabetes; Kidney Transplantation; Pancreas Transplantation
• Intervention / Treatment: Drug: Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus]

Detailed Description

The study will be conducted in 25 patients hospitalized at Nantes University Hospital. Tacrolimus will be started on the day of surgery (or on the day after) according to Nantes local standard doses and practices. After a stable trough level is achieved (on postoperative day 7-17) the first PK profile will be measured. Subsequently, the switch to ENVARSUS® will be performed (initial dose of 0.17 mg/kg/day) on a single morning oral dosage regimen. A second PK profile will be measured, between 7 to 14 days after initiation of ENVARSUS®. All these PK measurements will take place during the post-operative recovery in the hospital (typically 2-3 weeks). All patients will receive Thymoglobulin or Alemtuzumab induction, Myfortic or Cellcept (or generics), with or without prednisone according to local practices. Anti-infectious prophylaxis will be given according to Nantes local practices.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: DIEGO CANTAROVICH; Phone Number: +33 (0)2 40 08 74 40; Email: diego.cantarovich@chu-nantes.fr

Study Locations

• France
  • Nantes, France, 44093
    • Nantes University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient is willing and able to give informed consent for participation in the trial.
• Male or Female, aged 18 years or above.
• Type I Diabetics patients with end stage chronic renal failure
• Recipient of kidney and pancreas-transplant
• At least one of the two transplants are functioning at time of PK profile measurements : a patient with early pancreatic graft failure due to thrombosis may be included if the kidney is well functioning
• Standard immunosuppressive therapy has been started post-operatively, in accordance with local policy, including tacrolimus.
• In the Investigator's opinion, is able and willing to comply with all trial requirements.
• Patients with social security.

Exclusion Criteria:

The participant may not enter the trial if ANY of the following apply:

• Patient is inappropriate for standard immunosuppressive therapy.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the patients at risk because of participation in the trial, or may influence the result of the trial, or the patient's ability to participate in the trial.
• Concomitant therapy with drugs potentially interfering with tacrolimus pharmacokinetics, especially those interfering with CYP3A4 (see 4.4 section in tacrolimus / ENVARSUS® summary of product characteristics).
• Loss of the pancreatic graft due to immunological causes
• Pregnant or breast-feeding women and female patient with potential childbearing refusing contraception.
• Vulnerable people: persons deprived of liberty; under trusteeship or under curatorship.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tacrolimus then Envarsus; Tacrolimus will be started on the day of surgery. After a stable trough level is achieved (on postoperative day 7-17) the first PK profile will be measured. Subsequently, the switch to ENVARSUS® will be performed

Drug: Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus]; Phase 1: standard dose and frequency tacrolimus, used in accordance with licensing and local protocols. Suitable target trough level should be between 7-14 ng/ml. Phase 2: ENVARSUS® (LCP Tacro - extended release tacrolimus), used once-daily at an initial dose of 0.17mg/kg, dose adjusted to maintain an appropriate therapeutic blood concentration (measured by trough level). Suitable target trough level should be between 7-14 ng/ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterise the bioavailability of Envarsus® and compare it to the bioavailability of tacrolimus	To characterise the PK profile of extended release tacrolimus (Envarsus®) in diabetic transplant recipients, and compare it to the PK profile of tacrolimus : bioavailability AUC0-24	Initial tacrolimus PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® PK profile measurement: day 15-32 post SPK transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts: Cmin	Cmin	Initial tacrolimus and myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis.: Cmin	Cmin	Initial tacrolimus and myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts : Cmax	Cmax	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis.: Cmax	Cmax	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts: Cavg	Cavg	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myforticin patients only with a functional kidney graft in case of early pancreas thrombosis.: Cavg	Cavg	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts: Tmax	Tmax	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis..: Tmax	Tmax	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts : Ke	Ke	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis.: Ke	Ke	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts : t1/2	t1/2	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis.: t1/2	t1/2	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts: % fluctuation	% fluctuation	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients only with a functional kidney graft in case of early pancreas thrombosis: % fluctuation	% fluctuation	Initial tacrolimus and Myfortic PK profile measurement: day 7-17 post SPK transplantation. Second ENVARSUS® and Myfortic PK profile measurement: day 15-32 post SPK transplantation
Assessment of biological and clinical tolerance/ safety: Incidence of serious adverse events	Incidence of serious adverse events	Months 6, or on leaving hospital if after 6 months (maximum one year after the inclusion)

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: DIEGO CANTAROVICH, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Actual): November 7, 2023
• Study Completion (Actual): November 7, 2023

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Tacrolimus; kidney transplant; pancreas 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: RC19_0247

Drug and device information, study documents

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