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

Ph3,DB/DD,Multi-Ctr,Pros,Rand Study-Efficacy and Safety of LCP-Tacro™ Tablets, QD, Compared to Prograf® Capsules,BID, in Combination With Mycophenolate Mofetil for Acute Allograft Rejection in De Novo Kidney Transplant

This study will evaluate the efficacy and safety of LCP-Tacro (tacrolimus) Tablets administered once-a-day compared to Prograf (tacrolimus) Capsules twice-a-day as immunosuppression for the prevention of organ rejection in newly transplanted adult kidney transplant recipients. Patients will be treated for a 12 month study period followed by a 12 month, blinded extension treatment period To show that LCP-Tacro Tablets are clinically similar to Prograf Capsules in the prevention of acute rejection.

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:

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

Exclusion Criteria:

1. Recipients of any non-renal transplant (solid organ or bone marrow) ever
2. Panel reactive antibody (PRA) >30%
3. Patients with any condition that may affect study drug absorption (e.g. gastrectomy or clinically significant diabetic gastroenteropathy)
4. Body mass index (BMI) 18 kg/m2
5. History of alcohol abuse
6. History of recreational drug abuse
7. Screening 12-lead electrocardiogram (ECG) demonstrating clinically relevant abnormalities
8. WOCBP who are either pregnant, lactating, planning to become pregnant
9. Patients with an oral temperature (prior to study drug dosing) of 38.0 ºC (100.4 ºF) or higher
10. Patients with clinically significant active infections
11. Patients with a known hereditary immunodeficiency
12. Patients with malignancies or with a history of malignancies (within the last 5 years)
13. Patients who are receiving or expect to receive sirolimus, everolimus, azathioprine,or cyclophosphamide within 3 months prior to enrollment
14. Patients with evidence of clinically significant disease (e.g., cardiac, gastrointestinal or hepatic disorders)
15. Patients with reversible cardiac ischemia (history of untreated reversible ischemia on stress test)
16. Patients with clinically symptomatic congestive heart failure or documented ejection fraction of less than 45%
17. Patients with significant chronic obstructive pulmonary disease, pulmonary restrictive disease or significant pulmonary hypertension
18. Treatment with an investigational drug, device or regimen within 1 year preceding the first dose of study drug
19. Patients who are unwilling to refrain from consumption of grapefruit or grapefruit containing juices
20. Patients receiving concomitant drugs that may affect concentrations of tacrolimus in whole blood, as listed in Appendix 2
21. Laboratory variables that are abnormal (outside laboratory reference range) and clinically relevant, as judged by the Investigator
22. 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).
23. Patients who experienced graft loss within 1 year of transplant, due to acute rejection or due to BK nephropathy
24. Patients having experienced focal segmental glomerulosclerosis (FSGS)
25. Donor with positive serological test result for HIV-1, HBV or HCV
26. Donor with history of malignant disease (current or historical)
27. Centers for Disease Control and Prevention high-risk donor
28. Patients with mental dysfunction or inability to cooperate with the study
29. Cold ischemia time >30 hours

29. Non-heart-beating donor