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

NCT ID: NCT04496401

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2023-11-07

Brief Summary

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.

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.

Conditions

Kidney Transplantation; Pancreas Transplantation; Diabetes

Keywords

Tacrolimus; kidney transplant; pancreas transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus]

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

DIEGO CANTAROVICH

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

Nantes University Hospital

Nantes, , France

Countries

France

Other Identifiers

RC19_0247

Identifier Type: -

Identifier Source: org_study_id