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

NCT04496401 | Completed Phase 4

• 1 other identifier: RC19_0247
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplantation; Pancreas Transplantation; Diabetes

Keywords

Tacrolimus; kidney transplant; pancreas transplant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Further quantification of the PK profile of extended release tacrolimus and Myfortic in patients with both functional grafts: 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

  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

  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

  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

  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

Study Arms (1)

Tacrolimus then Envarsus

EXPERIMENTAL

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]

Interventions

Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus] 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.

Tacrolimus then Envarsus

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nantes University Hospital: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

Nantes University Hospital

Nantes, 44093, France

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• DIEGO CANTAROVICH

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: August 3, 2020
• Study Start: September 28, 2020
• Primary Completion: November 7, 2023
• Study Completion: November 7, 2023
• Last Updated: December 14, 2023

Record last verified: 2023-05

Locations

FR (1)