Pharmacokinetics of LCP-Tacro in Stable Liver Transplant Patients

NCT00608244 | Completed Phase 2 Results

• 1 other identifier: LCP Tacro 2012
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

A three sequence, open-label, multi-center, prospective, study in stable liver transplant patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules.

Conditions

Liver Failure

Keywords

Tacrolimus; Pharmacokinetics; Liver Transplantation

Outcome Measures

Primary Outcomes (5)

• Evaluation of Steady State Tacrolimus Trough Levels (C24).

  Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.

  7 Days

• Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).

  Patients had a baseline AUC measured (0 to 24 hours) at day 7 before conversion to LCP-Tacro. The following time points were used to obtain the PK curve for Prograf on day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 15, 16, 20 and 24 hours after the morning dose.

  7 Days

• Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).

  Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, a trough level (C24) was measured.

  21 Days

• Evaluation of Steady State Tacrolimus Exposure (AUC 0-24) on Day 21.

  Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours). The following time points were used to obtain the PK curve for LCP-Tacro on day 21: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours post-dose.

  21 Days

• Safety Evaluation

  A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.

  52 days

Study Arms (1)

LCP-Tacro

EXPERIMENTAL

Prograf was administrated BID, doses per product labeling, with an interval of 12±1 hours between the morning and evening doses. Patients continued on the same dose from Day 0 through Day 7. On Day 8, all patients were converted to LCP Tacro QD for 14 Days with one fixed dose change allowed at Day 15. LCP-Tacro was administered orally once daily in the morning, with an interval of 24 ± 1 h between doses. Trough levels were to be maintained within predefined therapeutic ranges of 5 to 15 ng/mL. LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.

Drug: LCP Tacro; Drug: Prograf

Interventions

LCP Tacro DRUG

In the morning of Day 8 (after completing one week treatment with Prograf), all patients will be converted to LCP Tacro QD with a conversion ratio of 0.66-0.8. LCP-Tacro will be administered for 14 Days with one fixed dose change allowed at Day 15. LCP-Tacro will be administered orally once daily in the morning, with an interval of 24 ± 1 h between doses. Trough levels were to be maintained within predefined therapeutic ranges of 5 to 15 ng/mL.

Also known as: tacrolimus

LCP-Tacro

Prograf DRUG

Prograf will be administrated twice a day, per product labeling, with an interval of 12 ± 1 hours between the morning and evening doses. Patients will continue on the same dose on Day 0 through Day 7 to maintain target trough levels of 5-12 ng/mL.

Also known as: Tacrolimus

LCP-Tacro

Eligibility Criteria

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

You may qualify if:

• Men and women 18-65 years of age who are recipients of a liver transplant at least six months prior to enrollment
• Patients on oral Prograf therapy as part of their maintenance immunosuppression therapy, with stable doses and trough levels of tacrolimus of 5-12 ng/mL for at least four weeks prior to enrollment with at least two measurements at least two days apart in the screening period up to fourteen days prior to enrollment
• Concurrent immunosuppression with mycophenolate mofetil (MMF, CellCept) or mycophenolic acid delayed-release tablets (Myfortic) is allowed but patients on either of these medications should be on stable doses for at least four weeks prior to enrollment
• Patients with stable serum bilirubin, AST, ALT, and Alk Phos or GGT that are ≤ 2 times the upper limit of normal based on local laboratory criteria
• Patients with serum creatinine ≤2.0 mg/dL prior to enrollment
• Able to swallow study medication
• Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study protocol.
• Women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication and agree to use contraceptive measures to avoid pregnancy during participation in the trial.

You may not qualify if:

• Recipients of any transplanted organ other than a liver
• White blood cell count ≤ 2.8 x 109/L
• Patients who are receiving a total dose of Prograf \< 3 mg per 24 hours
• Patients who are receiving more than 10 mg of prednisone per day
• Patients unable or unwilling to provide informed consent
• Pregnant or nursing women
• Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception
• Administration of any other investigational agent in the three months prior to enrollment
• Patients receiving any drug interfering with tacrolimus metabolism
• Patients who have taken sirolimus within the three months prior to screening
• Patient with an episode of acute cellular requiring antibody therapy within the six months prior to enrollment
• Patients treated for acute cellular rejection within the thirty days prior to enrollment
• Patient who is HCV negative and has received an HCV positive (HCV RNA by PCR or HCV antibody) donor liver
• Patients presenting after liver transplantation with recurrent HCV infection, documented by presence of HCV RNA in serum and grade II or greater inflammation or stage II or greater fibrosis on liver biopsy
• Patients being actively treated with antiviral therapy, such as interferons or ribavirin, for recurrent hepatitis C.

Sponsors & Collaborators

• Veloxis Pharmaceuticals: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 44123, United States

Location

Related Publications (1)

• Alloway RR, Eckhoff DE, Washburn WK, Teperman LW. Conversion from twice daily tacrolimus capsules to once daily extended-release tacrolimus (LCP-Tacro): phase 2 trial of stable liver transplant recipients. Liver Transpl. 2014 May;20(5):564-75. doi: 10.1002/lt.23844. Epub 2014 Mar 26.

  PMID: 24493215 DERIVED

MeSH Terms

Conditions

Liver Failure

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Christina Sylvest
• Organization: Veloxis Pharmaceuticals A/S

csy@veloxis.com

+45 20553877

Study Officials

• Rita Alloway, PharmD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: February 6, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: August 28, 2015
• Results First Posted: August 28, 2015

Record last verified: 2015-08

Locations

US (1)