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

NCT02608606 | Completed DMC

• 1 other identifier: FKoral-sl
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Evidence of Liver Transplantation; Effects of Immunosuppressant Therapy

Outcome Measures

Primary Outcomes (1)

• Compare tacrolimus exposure using per oral and sublingual administration employing AUC (Area Under the Curve).

  compared oral administration versus sublingual administration of tacrolimus

  30 days

Secondary Outcomes (1)

• Compare tacrolimus dose necessary to obtain similar trough levels employing per oral and sublingual administration

  30 days

Study Arms (2)

oral administration of tacrolimus

NO INTERVENTION

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.

sublingual administration of tacrolimus

ACTIVE COMPARATOR

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

Interventions

Tacrolimus DRUG

compared oral administration versus sublingual administration of tacrolimus.

Also known as: FK506

sublingual administration of tacrolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Pontificia Universidad Catolica de Chile

Santiago, 8330024, Chile

Location

Related Publications (11)

• Agopian VG, Petrowsky H, Kaldas FM, Zarrinpar A, Farmer DG, Yersiz H, Holt C, Harlander-Locke M, Hong JC, Rana AR, Venick R, McDiarmid SV, Goldstein LI, Durazo F, Saab S, Han S, Xia V, Hiatt JR, Busuttil RW. The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center. Ann Surg. 2013 Sep;258(3):409-21. doi: 10.1097/SLA.0b013e3182a15db4.

  PMID: 24022434 RESULT

• Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Pharmacoeconomic study of tacrolimus-based versus cyclosporine-based immunosuppressive therapy following liver transplantation. Transplant Proc. 2001 Feb-Mar;33(1-2):1532-4. doi: 10.1016/s0041-1345(00)02585-9. No abstract available.

  PMID: 11267411 RESULT

• Collin C, Boussaud V, Lefeuvre S, Amrein C, Glouzman AS, Havard L, Billaud EM, Guillemain R. Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study. Transplant Proc. 2010 Dec;42(10):4331-7. doi: 10.1016/j.transproceed.2010.09.126.

  PMID: 21168693 RESULT

• Reams BD, Palmer SM. Sublingual tacrolimus for immunosuppression in lung transplantation: a potentially important therapeutic option in cystic fibrosis. Am J Respir Med. 2002;1(2):91-8. doi: 10.1007/BF03256598.

  PMID: 14720063 RESULT

• Reams D, Rea J, Davis D, Palmer S. Utility of sublingual tacrolimus in cystic fibrosis patients after lung transplantation. J Heart Lung Transplant. 2001 Feb;20(2):207-208. doi: 10.1016/s1053-2498(00)00447-2. No abstract available.

  PMID: 11250374 RESULT

• Romero I, Jimenez C, Gil F, Escuin F, Ramirez E, Fudio S, Borobia A, Carcas A. Sublingual administration of tacrolimus in a renal transplant patient. J Clin Pharm Ther. 2008 Feb;33(1):87-9. doi: 10.1111/j.1365-2710.2008.00884.x.

  PMID: 18211623 RESULT

• Srinarong P, Pham BT, Holen M, van der Plas A, Schellekens RC, Hinrichs WL, Frijlink HW. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration. Drug Dev Ind Pharm. 2012 Apr;38(4):490-500. doi: 10.3109/03639045.2011.613075. Epub 2011 Sep 30.

  PMID: 21961909 RESULT

• Tsapepas D, Saal S, Benkert S, Levine D, Delfin M, Cremers S, Amann S, Dadhania D, Kapur S, Aull M. Sublingual tacrolimus: a pharmacokinetic evaluation pilot study. Pharmacotherapy. 2013 Jan;33(1):31-7. doi: 10.1002/phar.1149.

  PMID: 23307542 RESULT

• van de Plas A, Dackus J, Christiaans MH, Stolk LM, van Hooff JP, Neef C. A pilot study on sublingual administration of tacrolimus. Transpl Int. 2009 Mar;22(3):358-9. doi: 10.1111/j.1432-2277.2008.00779.x. Epub 2008 Oct 30. No abstract available.

  PMID: 18980626 RESULT

• Watkins KD, Boettger RF, Hanger KM, Leard LE, Golden JA, Hoopes CW, Singer JP. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transplant. 2012 Feb;31(2):127-32. doi: 10.1016/j.healun.2011.10.015. Epub 2011 Dec 16.

  PMID: 22177691 RESULT

• Nasiri-Toosi Z, Dashti-Khavidaki S, Nasiri-Toosi M, Khalili H, Jafarian A, Irajian H, Abdollahi A, Sadrai S. Clinical pharmacokinetics of oral versus sublingual administration of tacrolimus in adult liver transplant recipients. Exp Clin Transplant. 2012 Dec;10(6):586-91. doi: 10.6002/ect.2012.0032. Epub 2012 Jul 5.

  PMID: 22770208 RESULT

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Carlos Benitez, Hepatologist

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 20, 2015
• Study Start: March 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: October 12, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

CL (1)