Liver FailurePhase 2NCT00772148
Pharmacokinetics of LCP-Tacro™ Once Daily and Prograf® Twice A Day in Adult De Novo Liver Transplant Patients
A Phase 2 study testing LCP -Tacro and Prograf in people with Liver Failure, run by Veloxis Pharmaceuticals at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Failure
- What is being tested?
- LCP -Tacro and Prograf
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Liver Failure
- Being tested
- LCP -Tacro, Prograf
- Keywords
- Liver, Hepatic, Transplantation, Immunosuppression, Tacrolimus, Prograf
- Medical subject headings
- Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCP -TacroDrug
Also called tacrolimus
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)
PrografDrug
Also called tacrolimus
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)
| Study group | Role | What they receive |
|---|---|---|
| LCP-Tacro | Experimental | LCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) Receives: Drug: LCP -Tacro |
| Prograf (tacrolimus) | Active comparator | Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) Receives: Drug: Prograf |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days
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.
Measured: 14 days
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.
Measured: 1 day
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.
Measured: 7 days
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.
Measured: 14 days
Secondary outcomes (1)
Number of Participants Who Died Within the 360 Days.
Number of patients who died was compared between the two groups during the study.
Measured: 360 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Veloxis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CTI Clinical Trial and Consulting Services, Aptuit
- Responsible party
- Sponsor
- Investigators
- Angel Alsina, M.D., Principal investigator, Tampa General Hospital, LifeLink Healthcare Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00772148
- Sponsor's protocol ID
- LCP-Tacro 2018
- Status last verified
- Jun 2015
- First submitted
- 14 Oct 2008
- Last updated
- 25 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 30667591
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00772148
- Acronym / sponsor ID
- LCP-Tacro 2018
- Conditions
- Liver Failure
- Keywords
- Liver, Hepatic, Transplantation, Immunosuppression, Tacrolimus, Prograf
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Veloxis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- CTI Clinical Trial and Consulting Services, Aptuit
- Study start
- Oct 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 15 Oct 2008 (estimated)
- Results
- Posted 25 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LCP-Tacro | Experimental | Drug: LCP -TacroLCP - Tacro™ tablets, once daily (LifeCycle Pharma A/S, Hørsholm DK) |
| Prograf (tacrolimus) | Active comparator | Drug: PrografPrograf® capsules, twice daily (Astellas Pharma US, Deerfield IL) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LCP -TacroAlso: tacrolimusLCP-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) | Drug | LCP-Tacro |
| PrografAlso: tacrolimusOral 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) | Drug | Prograf (tacrolimus) |
Primary outcome
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.
Time frame: 14 days
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.
Time frame: 14 days
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.
Time frame: 1 day
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.
Time frame: 7 days
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.
Time frame: 14 days
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.
1 secondary outcome
Number of Participants Who Died Within the 360 Days.
Time frame: 360 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30667591DuBay 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angel Alsina, M.D. principal investigator
Tampa General Hospital, LifeLink Healthcare Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LCP -Tacro and Prograf in people with Liver Failure, run by Veloxis Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 14 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00772148, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2015.