Pharmacokinetics of LCP-Tacro™ Once Daily and Prograf® Twice A Day in Adult De Novo Liver Transplant Patients

This study has been completed.
Sponsor:
Collaborators:
CTI Clinical Trial and Consulting Services
Aptuit Inc.
Information provided by (Responsible Party):
Veloxis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00772148
First received: October 14, 2008
Last updated: July 3, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to demonstrate the pharmacokinetics (PK, measuring the amount of medication in blood samples) and safety of a new medicine, LCP-Tacro™ tablets, and Prograf® capsules, a drug commonly taken by transplant recipients to prevent the body from rejecting a transplanted kidney and liver. LCP-Tacro is a tablet containing the same active ingredient (tacrolimus) that is in Prograf capsules, but the tablet has been designed to release tacrolimus over an extended period so that it only has to be taken once daily. LCP-Tacro is an investigational drug.

This study will evaluate the levels of tacrolimus in the blood in the first two weeks after a liver transplant in patients randomly assigned (by chance, like flipping a coin) to take either LCP-Tacro™ tablets (tacrolimus) once daily or Prograf® capsules twice daily. In addition, patients will remain on study drug for 360 days in order to evaluate the relative safety of LCP-Tacro™ tablets compared to Prograf over a longer period of time.


Condition Intervention Phase
Liver Transplantation
Drug: LCP - Tacro™ tablets
Drug: Prograf®
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multi-Center, Randomized Trial to Demonstrate the Pharmacokinetics of LCP-Tacro™ Tablets Once Daily and Prograf® Capsules Twice Daily in Adult De Novo Liver Transplant Patients

Resource links provided by NLM:


Further study details as provided by Veloxis Pharmaceuticals:

Primary Outcome Measures:
  • Pharmacokinetics of LCP-Tacro™ tablets in the first 14 days after transplantation in adult de novo liver recipients. [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparative pharmacokinetics. Efficacy death, graft loss, biopsy proven acute rejection) and safety of LCP-Tacro™ tablets and Prograf capsules within 360 days after liver transplantation. [ Time Frame: 360 days ] [ Designated as safety issue: Yes ]

Enrollment: 58
Study Start Date: October 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK)
Drug: LCP - Tacro™ tablets
Dosage is determined by monitoring tacrolimus whole blood trough levels
Other Name: LCP-Tacro
Active Comparator: 2
Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)
Drug: Prograf®
Dosage is determined by monitoring tacrolimus whole blood trough levels
Other Name: Prograf

Detailed Description:

This was a randomized, parallel-group, open-label, multicenter study in adult de novo liver transplant patients to demonstrate the pharmacokinetics and safety of once-daily treatment of LCP-Tacro tablets and twice-daily Prograf capsules in the first 2 weeks after live transplantation. The study also compared the efficacy and safety of LCP-Tacro and Prograf over an additional 50 weeks after liver transplantation. Eligible patients were randomized (1:1 ratio) within 72 hours after transplantation (graft reperfusion) to receive either: 1) LCP-Tacr tablets orally once daily (QD) in the morning, with an interval of 24 +/- 1 hours between dosed, starting at 0.07 to 0.11 mg/kg (the starting daily dose for African-American patients was 0.09 to 0.13 mg/kg), or 2) Prograf capsules in 2 equally divided morning and evening doses, starting at 0.10 to 0.15 mg. Subsequent doses of study medications were to be adjusted by the investigator according to local practice to maintain a target whole blood tacrolimus trough level of 5 to 20 ng/mL thought Day 14. Twenty-four-hour pharmacokinetic assessments were performed on Days 1, 7 and 14; additionally whole blood tacrolimus trough levels for statistical analysis were measured on Days 2, 3, 4, 7, 10, 12, 12, 42, 90, 120, 180, 270, and 360. Physicians could also perform tacrolimus trough levels at other times at their discretion. On Day 360, the patients were placed on maintenance immunosuppressive regimen determined by their treating physician. Following completion of the third and final pharmacokinetic assessment on Day 14, patients entered the maintenance phase (Days 15 to 360) of study and remained on their assigned study medication until Day 360. Visits for safety assessments and tacrolimus trough levels during the maintenance phase were on Days 42, 90, 120, 180, 270 and 360.

Immunosuppressive therapy after the conclusion of the study was to be administered at the discretion of the patient's population.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult men and women at least 18 years of age who are recipients of a liver transplant from a deceased donor with a Model for End-Stage Liver Disease (MELD) score at the time of transplantation of ≤ 30 who are able to give informed consent for participation

Exclusion Criteria:

  • Recipient of any transplanted organ other than a liver
  • Recipients of a liver from a non-heart beating donor
  • Recipients of a liver from an ABO incompatible donor
  • Recipients of a bone marrow or stem cell transplant
  • Patients with a white blood cell count ≤ 2.8 x 109/L unless the absolute neutrophil count (ANC) is > 1.0 x 109/L
  • Patients who fail a drugs of abuse screen in the pre-transplant evaluation
  • Patients unable to swallow study medication
  • Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent, or who are unwilling to comply with the study protocol
  • Pregnant or nursing women (women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication)
  • Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception throughout the duration of the study
  • Patients who were treated with any other investigational agent in the 30 days prior to enrollment
  • Patients seropositive for human immunodeficiency virus (HIV)
  • Patients with a current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully, or hepatocellular carcinoma (HCC) that meet the Milan Criteria for liver transplantation
  • Patients with uncontrolled concomitant infection, a systemic infection requiring 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 may affect the absorption of tacrolimus
  • Patients with a known hypersensitivity to tacrolimus
  • Patients with any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator

Randomization to one of two treatment groups will be done post transplantation provided that the patient fulfills the following additional criteria:

  • Patient is able to receive their first dose of randomized study drug orally within 72 hours after the transplant surgery (graft reperfusion)
  • Patient was NOT given intravenous tacrolimus prior to their first oral dose of study medication
  • Recipient of a liver with a cold ischemia time of ≤ 10 hours
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772148

Locations
United States, Florida
LifeLink Healthcare Institute
Tampa, Florida, United States, 33606
Sponsors and Collaborators
Veloxis Pharmaceuticals
CTI Clinical Trial and Consulting Services
Aptuit Inc.
Investigators
Principal Investigator: Angel Alsina, M.D. Tampa General Hospital, LifeLink Healthcare Institute
  More Information

No publications provided

Responsible Party: Veloxis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00772148     History of Changes
Other Study ID Numbers: LCP-Tacro 2018
Study First Received: October 14, 2008
Last Updated: July 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Veloxis Pharmaceuticals:
Liver
Hepatic
Transplantation
Immunosuppression
Tacrolimus
Prograf

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014