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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

Tracking Information
First Submitted Date  ICMJE November 3, 2015
First Posted Date  ICMJE November 20, 2015
Last Update Posted Date October 12, 2016
Study Start Date  ICMJE March 2015
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2015)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors
Official Title  ICMJE Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Evidence of Liver Transplantation
  • Effects of Immunosuppressant Therapy
Intervention  ICMJE Drug: Tacrolimus
compared oral administration versus sublingual administration of tacrolimus.
Other Name: FK506
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Tacrolimus
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

-

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02608606
Other Study ID Numbers  ICMJE FKoral-sl
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Pontificia Universidad Catolica de Chile
Study Sponsor  ICMJE Pontificia Universidad Catolica de Chile
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Carlos Benitez, Hepatologist Pontificia Universidad Catolica de Chile
PRS Account Pontificia Universidad Catolica de Chile
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP