Crossover Study to Compare PK of Once Daily LCP-Tacro Tablets to Generic Tacrolimus Capsules Twice Daily.

Study Overview
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Brief Summary
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Open label, prospective, single-center, randomized, two sequence, three period crossover study to compare the steady state pharmacokinetics of LCP-Tacro tables to generic tacrolimus capsules administered twice daily in stable African-American renal transplant patients.

Detailed Description
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This is open label, prospective, single-center, randomized, two sequence, three period crossover study to compare the steady state pharmacokinetics of once daily dosing of LCP-Tacro tablets to tacrolimus capsules administered twice daily in stable African American kidney transplant patients. Approximately 72 male and female African American renal transplant patients on table immunosuppression regimens will be randomly assigned in a 1:1 ratio to one of two sequences: Sequence 1: (n=36) 18 patients requiring less than 0.15 mg/kg/day and 18 patients requiring equal to or greater than 0.15 mg/kg/day. Patients will continue on generic tacrolimus capsules on days 1-7 (24 hours PK profile on day 7) then patients are switched to LCP-Tacro tablets (at 15% lower dose of twice daily generic tacrolimus) on day 8. Sequence 2: (n=36) 18 patients requiring less than 0.15 mg/kg/day and 18 patients requiring equal to or greater than 0.15 mg/kg/day. Patients will receive LCP-Tacro tablets (at 15% lower dose than generic tacrolimus twice daily formulation) on days 1-7 (24 hour PK profile on day 7) patients are switched back to twice daily generic tacrolimus treatment beginning on day 8.

Official Title
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Prospective, Rand, Open-label, Single-center, 2 Sequence, 3 Period Crossover Study to Compare the Steady State PK of Once-Daily-Extended Release LCP-Tacro to Generic Tacrolimus Capsules Twice Daily in Stable A A Renal Transplant pt.

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: LCP-Tacro
* Drug: Tacrolimus -IR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥18-80 old, male or female African Americans Willing to give written informed consent and to comply with study visits and restrictions, including being able to speak, write and understand English Pt who have received a primary or secondary transplant Pt least 6 (six) mth post-transplant and on a stable dose of tacrolimus BMI ≥19 Pt who are sero-positive for Hepatitis B or C positive may also be enrolled Pt maintained on concurrent immunosuppression with stable doses during screening Pt on a proton PPI remain on the same PPI formulation and dose during the PK portion of the study. During PK phase Only: Pt taking any medication that could interfere with tacrolimus blood levels, including prescription and over-the-counter medications, herbal or food supplements (including grapefruit, and pomegranate products), or medications must continue the same dose and are willing to continue the same dose/routine During PK phase Only: the patient is not scheduled to begin any new medication that could interfere with tacrolimus blood levels, including prescription and over-the-counter medications, herbal or food Exclusion Criteria: Evidence of acute rejection episode within the past three months Pt not Africa-American Recipients of organ transplants other than kidney Known to be HIV positive at transplant Pt with recurrent focal segmental glomerulosclerosis (FSGS) Pt with any severe medical condition (including infection) requiring acute or chronic treatment Pt with a positive DSA Pt with a positive BK virus results GFR < 25 ml/min measured by MDRD4 as SOC within last 30 days Patients with AST, ALT, total bilirubin > 2.5 x ULN or evidence of severe liver disease Pt with WBC < to 2000/mm3 or ANC < to 1500 mm3 with PLT < 75,000/mm3 or HGB < 8 g/dl Pt with mental or physical conditions or known non-adherence Presence of intractable immunosuppressant complications of side effects resulting in dose adjustment of tacrolimus Exposed to investigational therapy within 30 days prior to enrollment No anticipated changes in the immunosuppressive regimen, other than those specified by the study protocol Pt with severe diabetic gastroparesis or other severe GI disturbances Pt who have underwent gastric banding or gastric bypass at any time pre or post-transplant Pregnant or nursing (lactating) women, or planning to become pregnant Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant who are unwilling to use a defined SOC of method

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LCP-Tacro<br>Envarsus XR | Drug: LCP-Tacro<br>* once-daily extended release tablet<br>* Other names: Envarsus XR;|
| Active Comparator: Tacrolimus - IR<br>Tacrolimus | Drug: Tacrolimus -IR<br>* twice daily capsules<br>* Other names: Generic Tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of AUC(0-24) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 7 | 
| Evaluation of C(Max) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 7 | 
| Evaluation of C(Min) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 7 | 
| Evaluation of AUC(0-24) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 14 | 
| Evaluation of C(Max) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 14 | 
| Evaluation of C(Min) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours | Day 14 | 
| Evaluation of AUC(0-24) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 21 | 
| Evaluation of C(Max) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate C(max). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 21 | 
| Evaluation of C(Min) for Envarsus XR and IR-Tac | Tacrolimus whole blood concentrations obtained from the central lab was used for PK analysis. Actual sampling time was used to calculate AUC(0-24). Arithmetic mean and standard deviation is given below. Nominal time points used were: Pre-dose (C0) and then 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 13, 14, 16, 18 and 24 hours. | Day 21 |