Pharmacokinetics of LCP-Tacro in Stable Kidney Transplant Patients

A Phase II, Open-Label, Multi-Center Prospective, Conversion Study in Stable Kidney Transplant Patients to Compare the Pharmacokinetics of LCP-Tacro Tablets Once-A-Day to Prograf® Capsules Twice-A-Day

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.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: LCP Tacro (tacrolimus); Drug: Prograf

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Hospital Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

ACTIVE_COMPARATOR: 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.

Drug: LCP Tacro (tacrolimus); Prograf will be administrated twice a day, per product labeling, with an interval of 12 ± 1 hours between the morning and evening doses. Patients will continue on the same dose on Day0 through Day 7 to maintain target trough levels of 7-12 ng/mL. On the morning of Day 8, following the final blood draw for the PK assessment, patient will be converted to LCP-Tacro using the conversion Ratio 0.66-0.8. LCP-Tacro tablets will be administered orally once daily in the morning, with an interval of 24 ± 1 hours between doses. Other Names: Tacrolimus modified-release LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.; Other Names: tacrolimus; Drug: Prograf; Prograf will be administrated twice a day, per product labeling, with an interval of 12 ± 1 hours between the morning and evening doses. Patients will continue on the same dose on Day0 through Day 7 to maintain target trough levels of 7-12 ng/mL. On the morning of Day 8, following the final blood draw for the PK assessment, patient will be converted to LCP-Tacro using the conversion Ratio 0.66-0.8. LCP-Tacro tablets will be administered orally once daily in the morning, with an interval of 24 ± 1 hours between doses. Other Names: Tacrolimus modified-release LCP-Tacro tablets were provided in 3 strengths: 1 mg, 2 mg, and 5 mg oral tablets.; Other Names: Tacrolimus

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Collaborators: CTI Clinical Trial and Consulting Services
• Investigators: Study Director: Alan Glicklich, MD, Veloxis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ACTUAL): March 1, 2008
• Study Completion (ACTUAL): March 1, 2008

Study Registration Dates

• First Submitted: July 2, 2007
• First Submitted That Met QC Criteria: July 2, 2007
• First Posted (ESTIMATE): July 4, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): July 23, 2015
• Last Update Submitted That Met QC Criteria: June 25, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Tacrolimus; Kidney Transplantation
• 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 2011