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

Renal Failure Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01962922
• Other study ID #: LCP-Tacro 3004
• Status: Completed
• Phase: Phase 3
• Start date: November 2013
• Est. completion date: August 2015

Study information

• Verified date: May 2018
• Source: Veloxis Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Failure
• Renal Insufficiency

Intervention

Drug:
• LCP-Tacro
once-daily extended release tablet
• Tacrolimus -IR
twice daily capsules

Locations

Country	Name	City	State
United States	University of Illinois, Chicago	Chicago	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washingto University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Veloxis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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