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

Phase 3

Completed

Conditions: Renal Failure

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

Registration Number: NCT01187953

Lead Sponsor: Veloxis Pharmaceuticals

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 543

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prograf (tacrolimus)	Prograf (tacrolimus)	Starting total daily dose of 0.10 mg/kg administered in two equally divided doses, morning and evening, per product labeling. Doses will be adjusted according to whole blood tacrolimus trough levels. In the initial post-transplant period, plasma trough levels will be measured at 24 and 48 hours. Study drugs will be adjusted to maintain the whole blood pre-dose (trough) concentration of tacrolimus in the target range of 6 - 11 ng/mL for the first 30 days, then 4 - 11 ng/mL for the remainder of the study.
LCP-Tacro	LCP-Tacro	The initial dose of 0.17 mg/kg will be administered orally in the morning (before noon) within 24 hours following transplantation. Subsequent doses will be adjusted according to whole blood tacrolimus trough levels.

Primary Outcome Measures

Name	Time	Method
The Primary Efficacy Endpoint for the Study is the Proportion of Treatment Failures Within 12 Months After Randomization to Study Drug.	360 days	Treatment failure is a composite endpoint; a patient is considered a treatment failure if the patient experienced any of the following events during this period: death, graft failure, BPAR (Banff grade ≥1A) or lost to follow-up.

Secondary Outcome Measures

Name	Time	Method
For the 24-month Analysis, the Endpoint Includes Additional Treatment Failures That Occurred During the 12-month Treatment Extension Period, up to Day 734 After the Randomization Date.	734 days	Treatment failure is a composite endpoint; a patient is considered a treatment failure if the patient experienced any of the following events during this period (day 1 to day 734): death, graft failure, BPAR (Banff grade ≥1A) or lost to follow-up.

Trial Locations

Locations (86): Clinical Site 1020
🇺🇸
Birmingham, Alabama, United States
Clinical Site 1031
🇺🇸
Loma Linda, California, United States
Clinical Site 1009
🇺🇸
Los Angeles, California, United States
Clinical Site 1022
🇺🇸
Sacremento, California, United States
Clinical Site 1045
🇺🇸
San Diego, California, United States
Clinical Site 1049
🇺🇸
San Diego, California, United States
Clinical Site 1044
🇺🇸
San Francisco, California, United States
Clinical Site 1011
🇺🇸
Denver, Colorado, United States
Clinical Site 1003
🇺🇸
New Haven, Connecticut, United States
Clinical Site 1036
🇺🇸
Gainesville, Florida, United States
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Clinical Site 1020
🇺🇸Birmingham, Alabama, United States