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

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.

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.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: LCP-Tacro; Drug: Tacrolimus -IR

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois, Chicago
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washingto University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: LCP-Tacro; Envarsus XR	Drug: LCP-Tacro; once-daily extended release tablet; Other Names: Envarsus XR
ACTIVE_COMPARATOR: Tacrolimus - IR; Tacrolimus	Drug: Tacrolimus -IR; twice daily capsules; Other Names: Prograf; Generic Tacrolimus

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Investigators: Study Director: Leslie Callahan, RN, Veloxis Pharmaceuticals

Publications and helpful links

General Publications

• Trofe-Clark J, Brennan DC, West-Thielke P, Milone MC, Lim MA, Neubauer R, Nigro V, Bloom RD. Results of ASERTAA, a Randomized Prospective Crossover Pharmacogenetic Study of Immediate-Release Versus Extended-Release Tacrolimus in African American Kidney Transplant Recipients. Am J Kidney Dis. 2018 Mar;71(3):315-326. doi: 10.1053/j.ajkd.2017.07.018. Epub 2017 Nov 20.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: October 8, 2013
• First Submitted That Met QC Criteria: October 10, 2013
• First Posted (ESTIMATE): October 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: LCP-Tacro 3004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO