Dose optimization of tacrolimus using Bayesian prediction including pharmacogenetic variables in renal transplant patients.

Phase 1

Conditions: PROPHYLAXIS OF ALLOGRAFT REJECTION AFTER RENAL TRASPLANT.
MedDRA version: 19.0Level: PTClassification code 10038533Term: Renal transplantSystem Organ Class: 10042613 - Surgical and medical procedures
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2016-000340-34-ES

Lead Sponsor: HOSPITAL UNIVERSITARI DE BELLVITGE

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

? Adult patients (? 18 years).
? Recipients of a renal graft from a cadaveric or living donor with more than 6 months post-transplant evolution.
? Patients who received a non-interrupted stable oral dose of immediate release tacrolimus (Prograf / Adoport®) and have had stable TAC trough concentrations between 6-10ng / ml for at least 10 days (steady state conditions).
? Patients receiving allowed concomitant immunosuppressive medication : mofetil or sodium mycophenolate and corticosteroids.
? May receive induction therapy with basiliximab.
? Subjects must be willing to give written informed consent for the trial. If a subject can not give written informed consent, a legal representative can sign instead.
? Women of childbearing potential should have a negative pregnancy test result at the time of inclusion and accept the use of a medically acceptable method of contraception during the selection and while receiving medication specified in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

? Patients on dialysis or treatment of rejection after transplantation.
? Patients treated with substances with potential interaction with TAC, particularly potent inhibitors of CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampin or rifabutin).
? Patients with induction therapy with ATG or rituxumab.
? Patients participating in another clinical trial or who were treated with any investigational drug within 30 days prior to inclusion.
? Patients with liver disease.
? Patient or donor with a current diagnosis or history of malignancy within the last 5 years except non-metastatic basal or squamous cell skin carcinoma successfully treated.
? Pregnant or lactating women and all women of childbearing potential unless they use reliable contraception. A pregnancy test will be performed in the selection and end of the study.
? Recipient of any other organ apart from kidney.
? Recipients of bone marrow or stem cell transplant.
? Recipients of a kidney from a ABO incompatible donor.
? Patients with donor specific anti-HLA antibodies.
? Anticipated cold ischemia time of ? 24 hours.
? Patients with a concomitant uncontrolled infection, systemic infection requiring treatment, or any other unstable medical condition that may interfere with the study objectives.
? Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of TAC.
? Patients with white blood cell count ? 2.8 x 109 / L unless the absolute neutrophil count (ANC) is ? 1.0 x 109 / L
? Patients with platelet count ? 50 x 109 / L.
? Patients with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding> 3 times the upper limit of normal during the 30 days prior to the transplant procedure.
? Patients with known hypersensitivity to TAC or any of the excipients in the formulation
? Patients unable to swallow study medication.
? Patients with any form of current substance abuse, psychiatric disorder or a condition that, in the investigator's opinion, may invalidate the communication with the investigator.
? Patients who require a high intake of potassium or potassium-sparing diuretics.
? Patients treated with substances with known nephrotoxic or neurotoxic effects.
? Recipients that are positive for hepatitis C virus (HCV-RNA positive) and / or hepatitis B virus (HBV DNA or HBsAg positive).
? Recipients positive for human immunodeficiency virus (HIV-Ab positive).
? Patients unable to understand the effects and risks of the study, who can not give informed consent in writing, or who are unwilling to comply with the study protocol patients.