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Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors (FKosl)

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ClinicalTrials.gov Identifier: NCT02608606
Recruitment Status : Completed
First Posted : November 20, 2015
Last Update Posted : October 12, 2016
Sponsor:
Information provided by (Responsible Party):
Pontificia Universidad Catolica de Chile

Brief Summary:
After liver transplantation one of the most important cost, for both patients and their health insurance system, is immunosuppressive drug therapy. Tacrolimus (FK 506) is considered the cornerstone of immunosuppressive therapy in solid organ transplantation. Oral administration is the usual route, however, sublingual (SL) administration has been recently reported. This method of administration avoids first pass metabolism and allows an alternative route after transplant surgery, particularly in those patients who should extend the period of fasting (prolonged intubation, ileus, etc). Interestingly, in some studies, the dose of tacrolimus SL required to maintain similar plasma concentrations compared with oral administration, is significantly lower, even up to 50%, which can result in considerable savings in short and long term. Among these studies, only one was conducted in liver recipients. This study suggest that SL administration of tacrolimus could allow to obtain similar concentrations compared with oral administration. The design of this study did not assess the existence of differences in the dose required and only included six patients.

Condition or disease Intervention/treatment Phase
Evidence of Liver Transplantation Effects of Immunosuppressant Therapy Drug: Tacrolimus Not Applicable

Detailed Description:

The patient will be scheduled fasting to liver transplant unit where the pharmacokinetic study was performed. After installation of the venous needle, blood samples will be collected on 4 ml tubes with EDTA as an anticoagulant at the following intervals of time in hours: 0 (immediately before the oral administration of tacrolimus); 0.5; 1.0; 1.5; 2; 4; 6; 9 and 12 h. post-dose. Once the blood samples taken, the tubes will be plugged, invest gently to mix with anticoagulant and stored at -20 ° C until analysis.

Subsequently, tacrolimus administration was change to sublingual route and dose was adjusted to obtain similar trough levels to those determined on per oral administration. The capsule be opened and its contents shall be deposited in the sublingual mucosa. To be ensure that drug will be absorted the patient will be instructed to insistently that after sublingual placement of the drug, should not swallow the capsule content for at least 15 minutes. The same pharmacokinetic study described for the oral route will be performed.

Breakfast will be administered 2 hours after ingesting the drug and lunch and dinner 6 and 10 hours after respectively. Fluid intake is discretionary.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors
Study Start Date : March 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
No Intervention: oral administration of tacrolimus
Oral administration of tacrolimus (FK506) in the usal dose and measuring plasmatic levels at hours 0, 0.5, 1, 2, 3, 4 and 6. Measuring AUC.
Active Comparator: sublingual administration of tacrolimus
sublingual administration of tacrolimus (FK506) in the dose that allows similar plasmatic level at time 0 compared with the oral administration, and measuring plasmatic levels at hours 0, 0.5, 1 , 2, 3 , 4 and 6. Measuring AUC.
Drug: Tacrolimus
compared oral administration versus sublingual administration of tacrolimus.
Other Name: FK506




Primary Outcome Measures :
  1. Compare tacrolimus exposure using per oral and sublingual administration employing AUC (Area Under the Curve). [ Time Frame: 30 days ]
    compared oral administration versus sublingual administration of tacrolimus


Secondary Outcome Measures :
  1. Compare tacrolimus dose necessary to obtain similar trough levels employing per oral and sublingual administration [ Time Frame: 30 days ]
    compared oral administration versus sublingual administration of tacrolimus



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Outline of immunosuppression that includes tacrolimus dosing every 12 hours.
  • Stable plasma levels of tacrolimus in 3 consecutive measurements.
  • Stable blood tests: biochemical profile, creatinine and liver profile.
  • Absence of treatment with drugs that have interaction with tacrolimus (antifungal and diltiazem) and use of grapefruit juice.
  • Absence of active bacterial or viral infection and rejection episodes within 8 weeks prior.

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02608606


Locations
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Chile
Pontificia Universidad Catolica de Chile
Santiago, Chile, 8330024
Sponsors and Collaborators
Pontificia Universidad Catolica de Chile
Investigators
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Principal Investigator: Carlos Benitez, Hepatologist Pontificia Universidad Catolica de Chile
Publications of Results:

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Responsible Party: Pontificia Universidad Catolica de Chile
ClinicalTrials.gov Identifier: NCT02608606    
Other Study ID Numbers: FKoral-sl
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: October 12, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The preliminary data from this trial will be presented at the AASLD Liver meeting in San Francisco in November 2015
Additional relevant MeSH terms:
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Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action