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

Primary Purpose

Liver Failure

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

LCP -Tacro

Prograf

About this trial

This is an interventional treatment trial for Liver Failure focused on measuring Liver, Hepatic, Transplantation, Immunosuppression, Tacrolimus, Prograf

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

LifeLink Healthcare Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LCP-Tacro

Prograf (tacrolimus)

Arm Description

LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK)

Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)

Outcomes

Primary Outcome Measures

Pharmacokinetics (Cmax and Cmin) of LCP-Tacro™ Compared to Prograf Early After Transplantations (Within the First 14 Days) in Adult de Novo Liver Transplant Recipients.

The pharmacokinetic parameters (Cmax and Cmin) were evaluated during the first 14 days after liver transplant (on days 1, 7 and 14). The results for Day 14 is listed below as the primary outcome parameter for this study.

Pharmacokinetics (AUC0-24) of LCP-Tacro™ Compared to Prograf Early After Transplantations (Within the First 14 Days) in Adult de Novo Liver Transplant Recipients.

The pharmacokinetic parameter (AUC, 0 to 24 hours post dose) was evaluated during the first 14 days after liver transplant (on days 1, 7 and 14). The results for Day 14 is listed below as the primary outcome parameter for this study.

Percentage of Patients in Each Treatment Group Achieving Sufficient Tacrolimus Whole Blood Trough Levels (5 to 20 ng/mL) During the First 14 Days Post-transplantation.

Percentage of patients with trough levels within the therapeutic range of 5 to 20 ng/mL was assessed during the initial 14 days (on days 1, 7 and 14) after liver transplant and compared between the two treatment groups.

Percentage of Patients in Each Treatment Group Achieving Sufficient Tacrolimus Whole Blood Trough Levels (5 to 20 ng/mL) During the First 14 Days Post-transplantation.

Secondary Outcome Measures

Number of Participants Who Died Within the 360 Days.

Number of patients who died was compared between the two groups during the study.

Full Information

NCT ID

NCT00772148

First Posted

October 14, 2008

Last Updated

June 2, 2015

Sponsor

Veloxis Pharmaceuticals

Collaborators

CTI Clinical Trial and Consulting Services, Aptuit

1. Study Identification

Unique Protocol Identification Number

NCT00772148

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

October 2008 (undefined)

Primary Completion Date

May 2010 (Actual)

Study Completion Date

May 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Veloxis Pharmaceuticals

Collaborators

CTI Clinical Trial and Consulting Services, Aptuit

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Failure

Keywords

Liver, Hepatic, Transplantation, Immunosuppression, Tacrolimus, Prograf

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

58 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LCP-Tacro

Arm Type

Experimental

Arm Description

LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK)

Arm Title

Prograf (tacrolimus)

Arm Type

Active Comparator

Arm Description

Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)

Intervention Type

Drug

Intervention Name(s)

LCP -Tacro

Other Intervention Name(s)

tacrolimus

Intervention Description

LCP-Tacro tablets will be administered orally once daily in the morning starting at 0.07 - 0.11 mg/kg. The starting dose for African-American patients will be 0.09 - 0.13 mg/kg. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL. Other Names:Tacrolimus modified-release LCP-Tacro™ tablets (0.5 mg, 1 mg, 2 mg, 5 mg)

Intervention Type

Drug

Intervention Name(s)

Prograf

Other Intervention Name(s)

tacrolimus

Intervention Description

Oral Prograf capsules will be administered starting at 0.10 - 0.15 mg/kg per day in two equally divided morning and evening doses. Subsequent doses of each study drug will be adjusted to maintain target whole blood tacrolimus trough levels of 5 - 20 ng/mL. Other name: tacrolimus Prograf® capsules (0.5 mg, 1 mg, 5 mg)

Primary Outcome Measure Information:

Title

Pharmacokinetics (Cmax and Cmin) of LCP-Tacro™ Compared to Prograf Early After Transplantations (Within the First 14 Days) in Adult de Novo Liver Transplant Recipients.

Description

Time Frame

14 days

Title

Pharmacokinetics (AUC0-24) of LCP-Tacro™ Compared to Prograf Early After Transplantations (Within the First 14 Days) in Adult de Novo Liver Transplant Recipients.

Description

Time Frame

14 days

Title

Percentage of Patients in Each Treatment Group Achieving Sufficient Tacrolimus Whole Blood Trough Levels (5 to 20 ng/mL) During the First 14 Days Post-transplantation.

Description

Time Frame

1 day

Title

Percentage of Patients in Each Treatment Group Achieving Sufficient Tacrolimus Whole Blood Trough Levels (5 to 20 ng/mL) During the First 14 Days Post-transplantation.

Description

Time Frame

7 days

Title

Percentage of Patients in Each Treatment Group Achieving Sufficient Tacrolimus Whole Blood Trough Levels (5 to 20 ng/mL) During the First 14 Days Post-transplantation.

Description

Time Frame

14 days

Secondary Outcome Measure Information:

Title

Number of Participants Who Died Within the 360 Days.

Description

Number of patients who died was compared between the two groups during the study.

Time Frame

360 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Angel Alsina, M.D.

Organizational Affiliation

Tampa General Hospital, LifeLink Healthcare Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

LifeLink Healthcare Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33606

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30667591

Citation

DuBay DA, Teperman L, Ueda K, Silverman A, Chapman W, Alsina AE, Tyler C, Stevens DR. Pharmacokinetics of Once-Daily Extended-Release Tacrolimus Tablets Versus Twice-Daily Capsules in De Novo Liver Transplant. Clin Pharmacol Drug Dev. 2019 Nov;8(8):995-1008. doi: 10.1002/cpdd.657. Epub 2019 Jan 22.

Results Reference

derived

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

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