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

Primary Purpose

Renal Failure

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
LCP-Tacro
Tacrolimus -IR
Sponsored by
Veloxis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Renal Failure

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Illinois, Chicago
  • Washingto University School of Medicine
  • Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

LCP-Tacro

Tacrolimus - IR

Arm Description

Envarsus XR

Tacrolimus

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
October 8, 2013
Last Updated
May 2, 2018
Sponsor
Veloxis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01962922
Brief Title
Crossover Study to Compare PK of Once Daily LCP-Tacro Tablets to Generic Tacrolimus Capsules Twice Daily.
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Veloxis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LCP-Tacro
Arm Type
Active Comparator
Arm Description
Envarsus XR
Arm Title
Tacrolimus - IR
Arm Type
Active Comparator
Arm Description
Tacrolimus
Intervention Type
Drug
Intervention Name(s)
LCP-Tacro
Other Intervention Name(s)
Envarsus XR
Intervention Description
once-daily extended release tablet
Intervention Type
Drug
Intervention Name(s)
Tacrolimus -IR
Other Intervention Name(s)
Prograf, Generic Tacrolimus
Intervention Description
twice daily capsules
Primary Outcome Measure Information:
Title
Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 7
Title
Evaluation of C(Max) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 7
Title
Evaluation of C(Min) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 7
Title
Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 14
Title
Evaluation of C(Max) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 14
Title
Evaluation of C(Min) for Envarsus XR and IR-Tac
Description
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
Time Frame
Day 14
Title
Evaluation of AUC(0-24) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 21
Title
Evaluation of C(Max) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 21
Title
Evaluation of C(Min) for Envarsus XR and IR-Tac
Description
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.
Time Frame
Day 21

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leslie Callahan, RN
Organizational Affiliation
Veloxis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Illinois, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Washingto University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29162334
Citation
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.
Results Reference
derived

Learn more about this trial

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

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