Safety and Efficacy of LCP-Tacro™ Once Daily in Stable Renal Transplant Patients Converted From Prograf® Twice Daily

Ph3, Open Label, Multi-Ctr, Pros, Rand Study -Efficacy and Safety, Conversion Prograf® Capsules BID to LCPTacro Tablets QD, for Prevent of Acute Allograft Rejection in Stable Kidney Transplant pt.

This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf® capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP Tacro™ tablets (tacrolimus, LifeCycle Pharma A/S, Hoersholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult kidney transplant patients. Patients on a stable dose of Prograf® will be randomly assigned to be converted from Prograf® twice daily to LCP Tacro™ once daily or to remain on maintenance therapy with Prograf® twice daily. Patients entering the study will be treated with assigned study drug and followed for one year for patient survival and the incidence of graft rejection or graft loss.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: LCP-Tacro; Drug: Prograf

Detailed Description

This is 2-armed parallel group, prospective, randomized, open-label, multicenter Phase 3 controlled trial to establish the efficacy and safety of conversion from maintenance immunosuppressive therapy with Prograf capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL) twice daily to maintenance immunotherapy with LCP-Tacro tablets (tacrolimus, LifeCycle Pharma A/S, Horsholm, Denmark) once daily for the prevention of acute allograft rejection in stable adult make and female kidney transplant patients. Recipients of kidney transplant 3 months to 5 years before Screening and on a stable dose of Prograf will be randomly assigned to be converted from Prograf twice daily to LCP-Tacro once daily or to remain on maintenance therapy with Prograf twice daily. There will be 11 study visits in the Treatment period.

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • California Institute of Renal Research/ Sharp Memorial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women at least 18 years of age who are recipients of a kidney transplant between 3 months and 5 years before the screening date
• Patients taking oral Prograf® capsules twice daily, at least 2 mg total dose per day, as part of their maintenance immunosuppression therapy, with tacrolimus trough levels of 5 to 15 ng/mL
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before receiving study drug

Exclusion Criteria:

• Recipients of any transplanted organ other than kidney
• Recipients of a bone marrow transplant
• Patients with an eGFR (MDRD7) < 30 mL/min at Screening
• Patients with a spot protein:creatinine ratio > 0.5
• Patients with a WBC count ≤ 2.8 ´ 109/L unless the WBC count has been stable for at least 2 weeks and the absolute neutrophil count is > 1.0 ´ 109 /L
• Patients unable to swallow study medication
• Patients incapable of understanding the purposes and risks of the study, who cannot give written informed consent and who are unwilling or unable to comply with the study protocol requirements
• Pregnant or nursing women
• Patients with reproductive potential who are unwilling/unable to use a double barrier method of contraception
• Patients who were treated with any other investigational agent within 3 months before Screening
• Patients who have taken sirolimus or everolimus within 3 months before Screening
• Patients on concurrent immunosuppression with MMF (CellCept) or MPS delayed-release tablets (Myfortic) who have not been on stable doses for at least 4 weeks before Screening
• Patients withdrawn from corticosteroids less than 30 days before Screening
• Patients with an episode of acute rejection requiring antibody therapy within 3 months before Screening
• Patients treated for acute rejection within 30 days before Screening
• Patients who are hepatitis C virus (HCV) negative who have received an HCV positive (HCV RNA by polymerase chain reaction or HCV antibody) donor kidney
• Patients seropositive for human immunodeficiency virus
• Patients with a current malignancy or a history of malignancy (within the past 5 years), except basal or nonmetastatic squamous cell carcinoma of the skin that has been treated successfully
• Patients with uncontrolled concomitant infection, a systemic infection requiring treatment, or any other unstable medical condition that could interfere with the study objectives
• Patients with severe diarrhea, vomiting, active peptic ulcer, or gastrointestinal disorder that may affect the absorption of tacrolimus
• Patients with 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCP-Tacro; LCP-Tacro tablets™, once daily (LifeCycle Pharma A/S, Hoersholm DK)	Drug: LCP-Tacro; LCP-Tacro tablets will be administered orally QD, at the same time in the morning to maintain trough levels at 5-15 ng/ML. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels. LCP-Tarco (tacrolimus) tablets provided in 0.5 mg, 1 mg, 2 mg, and 5 mg tablets.; Other Names: tacrolimus; tacrolimus modified release
Active Comparator: Prograf (tacrolimus); Prograf® capsules, twice daily (Astellas Pharma US, Deerfield IL)	Drug: Prograf; Oral prograf doses will be given BID (in the morning and evening), to maintain trough levels of 5- 15 ng/mL. Prograf capsules (tacrolimus) capsules, twice daily oral, provided in 0.5 mg, 1 mg, and 5 mg capsules.; Other Names: tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite Endpoint for Efficacy Failure Within 12 Months of Randomization: Death, Graft Failure, Biopsy-proven Acute Rejection or Loss to Follow-up.	12 months

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Collaborators: PPD
• Investigators: Principal Investigator: Steven Steinberg, M.D., Claifornia Institute of Renal Research/Sharp Memorial

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: December 19, 2008
• First Submitted That Met QC Criteria: January 2, 2009
• First Posted (Estimate): January 6, 2009

Study Record Updates

• Last Update Posted (Estimate): September 10, 2015
• Last Update Submitted That Met QC Criteria: August 11, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: kidney transplantation; tacrolimus; renal transplantation; maintenance immunosuppression; Prevention of acute allograft rejection
• 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 3001