Double-Blind,Double-Dummy,Efficacy/Safety,LCP-Tacro™ Vs Prograf®,Prevention Rejection,De Novo Adult Kidney Tx

This is a two-armed parallel group, prospective, randomized, double-blind, double-dummy,multicenter Phase 3 clinical study to establish the efficacy and safety of LCP-Tacro Tablets (tacrolimus, LifeCycle Pharma A/S, Hørsholm, Denmark) once daily for the prevention of allograft rejection in de novo adult male and female recipients of a primary or secondary kidney transplant evaluated by a combined efficacy endpoint comprised of acute rejection, graft loss and patient loss. The trial is designed to determine if the test drug, LCP-Tacro, is not inferior to an unacceptable extent to the reference compound, Prograf. Recipients of a kidney transplant who sign an informed consent form and fulfill all other inclusion and exclusion criteria will be randomly assigned to once-daily therapy with LCP-Tacro Tablets or to twice-daily therapy with Prograf Capsules (tacrolimus, Astellas Pharma US, Inc., Deerfield, IL), each concomitantly administered with mycophenolate mofetil (MMF) and corticosteroids. All patients will also receive interleukin-2 (IL-2) receptor antagonist (e.g.,Simulect®, basiliximab; Novartis Pharmaceuticals, East Hanover, NJ). Following screening,transplantation, and randomization, study visits will be conducted over a 12-month treatment period; with additional visits during a 12 month extension period on treatment and a follow-up safety assessment by visit or telephone interview 30 days after withdrawal from study drug.

Inclusion criteria

• informed consent
• 18 and 70 years, inclusive
• receiving primary or secondary renal allograft from a deceased donor or non-human leukocyte antigen (HLA) identical living donor
• no known contraindications to the administration of IL-2 receptor antagonist induction therapy, MMF, corticosteroids or tacrolimus
• negative pregnancy test
• Negative cross match test, and compatible (A, B, AB or O) blood type
• Able to swallow tablets and capsules

Exclusion criteria

• Recipients of any non-renal transplant (solid organ or bone marrow) ever
• Panel reactive antibody (PRA) >30%
• Patients with any condition that may affect study drug absorption (e.g. gastrectomy or clinically significant diabetic gastroenteropathy)
• Body mass index (BMI) 18 kg/m2
• History of alcohol abuse
• History of recreational drug abuse
• Screening 12-lead electrocardiogram (ECG) demonstrating clinically relevant abnormalities
• WOCBP who are either pregnant, lactating, planning to become pregnant
• Patients with an oral temperature (prior to study drug dosing) of 38.0 ºC (100.4 ºF) or higher
• Patients with clinically significant active infections
• Patients with a known hereditary immunodeficiency
• Patients with malignancies or with a history of malignancies (within the last 5 years)
• Patients who are receiving or expect to receive sirolimus, everolimus, azathioprine,or cyclophosphamide within 3 months prior to enrollment
• Patients with evidence of clinically significant disease (e.g., cardiac, gastrointestinal or hepatic disorders)
• Patients with reversible cardiac ischemia (history of untreated reversible ischemia on stress test)
• Patients with clinically symptomatic congestive heart failure or documented ejection fraction of less than 45%
• Patients with significant chronic obstructive pulmonary disease, pulmonary restrictive disease or significant pulmonary hypertension
• Treatment with an investigational drug, device or regimen within 1 year preceding the first dose of study drug
• Patients who are unwilling to refrain from consumption of grapefruit or grapefruit containing juices
• Patients receiving concomitant drugs that may affect concentrations of tacrolimus in whole blood, as listed in Appendix 2
• Laboratory variables that are abnormal (outside laboratory reference range) and clinically relevant, as judged by the Investigator
• Patients with positive results of any of the following serological tests: human immunodeficiency virus (HIV)-1 antibody, hepatitis B virus (HBV) surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb), and anti-hepatitis C virus (HCV)antibody (HCV Ab).
• Patients who experienced graft loss within 1 year of transplant, due to acute rejection or due to BK nephropathy
• Patients having experienced focal segmental glomerulosclerosis (FSGS)
• Donor with positive serological test result for HIV-1, HBV or HCV
• Donor with history of malignant disease (current or historical)
• Centers for Disease Control and Prevention high-risk donor
• Patients with mental dysfunction or inability to cooperate with the study
• Cold ischemia time >30 hours

• Non-heart-beating donor