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

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ClinicalTrials.gov Identifier: NCT01962922
Recruitment Status : Completed
First Posted : October 14, 2013
Results First Posted : August 15, 2016
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
Veloxis Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 8, 2013
First Posted Date  ICMJE October 14, 2013
Results First Submitted Date  ICMJE February 23, 2016
Results First Posted Date  ICMJE August 15, 2016
Last Update Posted Date June 6, 2018
Study Start Date  ICMJE November 2013
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2016)
  • Evaluation of AUC(0-24) for Envarsus XR and IR-Tac [ Time Frame: Day 7 ]
    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 [ Time Frame: Day 7 ]
    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 [ Time Frame: Day 7 ]
    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 [ Time Frame: Day 14 ]
    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 [ Time Frame: Day 14 ]
    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 [ Time Frame: Day 14 ]
    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 [ Time Frame: Day 21 ]
    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 [ Time Frame: Day 21 ]
    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 [ Time Frame: Day 21 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2013)
Pharmacokinetics [ Time Frame: 21 days ]
To evaluate the pharmacokinetics of LCP-Tacro in stable African American renal transplant patients compared to generic twice daily tacrolimus formulations.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2013)
Intra-patient variability [ Time Frame: After the first 21 days ]
  1. To evaluate intra-patients variability of tacrolimus pharmacokinetics.
  2. To confirm total daily dose (TDD) reduction in the LCP-Tacro group.
  3. Analysis of the impact of polymorphic genotype expression.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 10, 2013)
  • Safety and efficacy [ Time Frame: 180 days ]
    Analysis of safety and efficacy of LCP-Tacro tablets to generic tacrolimus capsules on stable renal transplant recipients.
  • quality of life [ Time Frame: 6 months ]
    Analysis of health-related quality of life, medication adherence and side effect profiles via surveys in patients on LCP-Tacro vs twice daily tacrolimus at randomization and at month 6 in each sequence group.
  • Pulse wave velocity [ Time Frame: 6 months ]
    Analysis of the pulse wave velocity (PWV) measurements in patients on LCP-Tacro vs twice daily tacrolimus measured at randomization and at 6 months in each sequence group.
  • Nephrotoxicity [ Time Frame: 6 months ]
    Analyses of markers for nephrotoxicity in patients on LCP-Tacro vs twice daily tacrolimus measuring endothelin-1 and TGF-Beta-1 drawn at randomization and at month 6 in each sequence group
  • Glucose tolerance [ Time Frame: 6 months ]
    Analyses of 2 hour oral glucose tolerance test (OGTT) in non-diabetic patients at randomization and at month 6 in each sequence group.
 
Descriptive Information
Brief Title  ICMJE Crossover Study to Compare PK of Once Daily LCP-Tacro Tablets to Generic Tacrolimus Capsules Twice Daily.
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Failure
Intervention  ICMJE
  • Drug: LCP-Tacro
    once-daily extended release tablet
    Other Name: Envarsus XR
  • Drug: Tacrolimus -IR
    twice daily capsules
    Other Names:
    • Prograf
    • Generic Tacrolimus
Study Arms  ICMJE
  • Active Comparator: LCP-Tacro
    Envarsus XR
    Intervention: Drug: LCP-Tacro
  • Active Comparator: Tacrolimus - IR
    Tacrolimus
    Intervention: Drug: Tacrolimus -IR
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 23, 2015)
50
Original Estimated Enrollment  ICMJE
 (submitted: October 10, 2013)
72
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01962922
Other Study ID Numbers  ICMJE LCP-Tacro 3004
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Veloxis Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Veloxis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Leslie Callahan, RN Veloxis Pharmaceuticals
PRS Account Veloxis Pharmaceuticals
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP