Conversion Pharmacodynamic Study in Stable Renal Transplant Patients Receiving Tacrolimus Two Times a Day to a New Formulation of Tacrolimus - LCP Tacro - 1 Time a Day.

NCT02961608 | Completed Phase 4

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

Brief Summary

LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability than twice-daily tacrolimus capsules and no new safety concerns.

• Stable kidney transplant patients can be safely converted from Adoport® twice-daily to LCP-Tacro®.
• The greater bioavailability of LCP-Tacro after once-daily dosing results in similar (AUC) exposure, at a dose approximately 30% less, than the total daily dose of Adoport®.
• LCP-Tacro provides a slow drug release and this results in flatter kinetics characterized by significantly lower peak-trough fluctuations.
• CN is the major cellular target of the calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus. The ability of these drugs to inhibit CN activity is dependent on their binding to the respective immunophilins, cyclophilins A and B for CsA and FKBP12 for tacrolimus.
• CN inhibition is a rate limiting phenomenon. Over concentrations of tacrolimus does not correlate with an increase in the CN activity.

Conditions

Kidney Transplant; Complications

Outcome Measures

Primary Outcomes (1)

• Area under the curve (AUC) of CN activity

  The main objective of this study is to compare the area under the curve (AUC) of CN activity after administration of a sustained release formulation (LCP- Tacro, Envarsus®) compared to an immediate release formulation (Prograf®) of TAC in renal transplant patients.

  Baseline and 35 days post conversion

Secondary Outcomes (3)

• Area Under the curve 0-24 h of each TAC formulation

  Baseline and 35 days post conversion

• TAC trough concentrations for optimal inhibition of CN

  Baseline and 35 days post conversion

• drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.

  Baseline and 35 days post conversion

Study Arms (1)

study group

EXPERIMENTAL

Drug: Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)

Interventions

Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®) DRUG

Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)

study group

Eligibility Criteria

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

You may qualify if:

• Adult patients (≥ 18 years).
• Receivers cadaveric renal graft or living donor with more than 6 months post-transplant evolution.
• Patients receiving Prograf stable and stable TAC trough concentrations between 5-10ng / ml non-interrupted oral dose for at least 10 days (steady state conditions).
• receiving concomitant immunosuppressive medication allowed: sodium or mycophenolate mofetil and corticosteroids.
• Subjects must be willing to give their written informed consent to testing and be able to do consent. If a subject can not give written informed consent independently, you can do your legal representative instead.

You may not qualify if:

• 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 liver disease.
• The patient or donor with the current diagnosis or history of malignancy within the past 5 years except carcinoma nonmetastatic basal or squamous cell skin treated successfully.
• pregnant or breast-feeding women and all women of childbearing age unless they use reliable contraception. A pregnancy test will be performed at screening and at the end of the study.
• Receiver of any other organ transplanted kidney.
• The recipients of bone marrow or stem cell transplant.
• Recipients of a kidney from a donor ABO incompatible.
• Patients with donor specific anti-HLA antibodies.
• Recipients of a kidney with anticipated cold ischemia time of ≥ 24 hours.
• Patients with concomitant uncontrolled infection, systemic infection in treatment, or any other unstable medical condition that could interfere with the study objectives.
• Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that can 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 levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding\> 3 times the upper limit of normal during the 30 days prior to the transplant procedure.

Sponsors & Collaborators

• Hospital Universitari de Bellvitge: lead

Study Sites (1)

Nephrology Department- Hospital Universitari Bellvtge

L'Hospitalet de Llobregat, Barcelona, 08028, Spain

Location

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: October 3, 2016
• First Posted: November 11, 2016
• Study Start: May 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: April 9, 2020

Record last verified: 2020-04

Locations

ES (1)