Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients

Phase 2

Completed

Conditions: Renal Failure

Interventions: Drug: LCP Tacro (tacrolimus)
Drug: Prograf

Registration Number: NCT00496483

Lead Sponsor: Veloxis Pharmaceuticals

Brief Summary: A three sequence, open-label, multi-center, prospective, study in stable kidney transplant patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules.

Detailed Description: A three sequence, open-label, multi-center, prospective, study in stable kidney transplant patients to assess and compare the pharmacokinetics (Cmax, C24, and AUC), and safety of LCP-Tacro (tacrolimus) tablets versus Prograf (tacrolimus) capsules.

Stable kidney transplant patients who fulfill all I/E criteria will be enrolled and kept on Prograf for 7 days. Following a 24-hour PK study on Day 7 to determine pharmacokinetics for Prograf, all patients will be converted to once daily LCP-Tacro for 7 days with no dose changes allowed. On Day 14 and Day 21 a 24-hour LCP-Tacro PK study will be performed. On Day 22 patients will be converted back to their original twice daily dose of Prograf for a safety follow-up period of 30 days ending with a safety assessment on day 53.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Men and women 18-65 years of age who are recipients of a renal transplant at least 6 months prior to enrollment
Patients on oral Prograf therapy as part of their maintenance immunosuppression therapy, with stable doses and trough levels of tacrolimus of 7-12 ng/mL for at least two weeks prior to enrollment.
Patients maintained on concurrent immunosuppression with mycophenolate mofetil (MMF, CellCept) or mycophenolic acid delayed-release tablets (Myfortic), with stable doses for at least two weeks prior to enrollment
Patients with serum creatinine < 2.0mg/dL prior to enrollment
Able to swallow study medication
Patients capable of understanding the purposes and risks of the study, who can give written informed consent and who are willing to participate in and comply with the study
Women of childbearing potential must have a negative serum pregnancy test within seven days prior to receiving study medication
Patients who successfully pass a drug screen

Exclusion Criteria

Recipients of any transplanted organ other than a kidney
White blood cell count < 2.8 x 10^9 /L
Patients who are receiving a total dose of Prograf for 24 hours < 3mg
Patients unable or unwilling to provide informed consent
Pregnant or nursing women
Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception
Administration of other investigational agent in the three months prior to enrollment
Patient receiving any drug interfering with tacrolimus metabolism
Patients who have taken sirolimus within the past three months prior to screening
Patient with an episode of acute cellular requiring antibody therapy within the 6 months prior to enrollment
Patient treated for acute cellular rejection within the 30 days prior to enrollment
Patient who is HCV negative and has received an HCV positive (HCV RNA by PCR or HCV antibody) donor kidney
Patient has a current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully
Patient has uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives
Patient has severe diarrhea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus
Patient will require therapy with any immunosuppressive agent other than those prescribed in the study
Patient has a known hypersensitivity to corticosteroids, mycophenolate mofetil, mycophenolic acid or tacrolimus
Patient has any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LCP-Tacro (tacrolimus)	LCP Tacro (tacrolimus)	Experimental: LCP Tacro; investigational product LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.
LCP-Tacro (tacrolimus)	Prograf	Experimental: LCP Tacro; investigational product LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.

Primary Outcome Measures

Name	Time	Method
Evaluation of Steady State Tacrolimus Trough Levels (C24).	7 days	Patients had a baseline trough level (C24) measured at day 7 before conversion to LCP-Tacro.
Evaluation of Steady State Tacrolimus Exposure Trough Levels (C24).	21 days	Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, a trough level (C24) was measured.
Evaluation of Steady State Tacrolimus Exposure (AUC 0-24).	21 days	Patients were converted from Prograf to LCP-Tacro on day 7. On day 21, AUC was measured (0 to 24 hours).

Secondary Outcome Measures

Name	Time	Method
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 21.	21 days	Cmax and Cavg was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 21.	21 days	Degree og fluctuation and degree of swing was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Cmax and Cavg) Was Measured at Day 7.	7 days	Cmax and Cavg was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Fluctuation and Swing) Was Measured at Day 7.	7 days	Degree og fluctuation and degree of swing was measured as baseline at day 7 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 21.	21 days	Tmax was measured at day 21 (Cmin was measured as part of the primary outcome).
Tacrolimus Pharmacokinetics (Tmax) Was Measured at Day 7.	7 days	Tmax was measured at baseline day 7 (Cmin was measured as part of the primary outcome).
Safety Evaluation	52 days	A combination of deaths, graft failure and biopsy proven acute rejections (BPAR) was used to evaluate the safety.