Double-Blind,Double-Dummy,Efficacy/Safety,LCP-Tacro™ Vs Prograf®,Prevention Rejection,De Novo Adult Kidney Tx (LCPTacro3002)

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.

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 543
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425APQ
    • Clinical Site 54163
  • Cordoba, Argentina, X5004CDT
    • Clinical Site 54164
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Clinical Site 61101
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Clinical Site 61105
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Clinical Site 61100
    • Parkville, Victoria, Australia, 3050
      • Clinical Site 61104
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Clinical Site 61102
    • Perth, Western Australia, Australia, 6000
      • Clinical Site 61106
• Brazil
  • Juiz de Fora, Brazil, 36036-330
    • Clinical Site 55178
  • Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
    • Clinical Site 55172
  • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
    • Clinical Site 55179
  • Ribeirao Preto, Brazil, 14048-900
    • Clinical Site 55175
  • Rio de Janeiro, Brazil, 21041-030
    • Clinical Site 55173
  • Sao Paulo, Brazil, 04038-002
    • Clinical Site 55171
• France
  • Brest, France, 29609
    • Clinical Site 33132
  • Nice, France, 06002
    • Clinical Site 33131
  • Saint Etienne, France, 42000
    • Clinical Site 33136
  • Toulouse, France, 31059
    • Clinical Site 33134
• Germany
  • Berlin, Germany, 10117
    • Clinical Site 49137
  • Essen, Germany, 45122
    • Clinical Site 49139
• Italy
  • Roma, Italy, 00133
    • Clinical Site 39144
• Korea, Republic of
  • Seoul, Korea, Republic of, 138736
    • Clinical Site 92113
• Mexico
  • Aguascalientes, Mexico, 20230
    • Clinical Site 52184
  • Cuernavaca, MOR, Mexico, 62448
    • Clinical Site 52181
  • Mexico City, Mexico, 14000
    • Clinical Site 52183
  • Mexico City, Mexico, 14080
    • Clinical Site 52182
• New Zealand
  • Auckland, New Zealand, 1142
    • Clinical Site 64112
  • Wellington South, New Zealand, 6021
    • Clinical Site 64121
• Poland
  • Bydgoszcz, Poland, 85-064
    • Clinical Site 48151
  • Szczecin, Poland, 70-111
    • Clinical Site 48148
  • Warszawa, Poland, 02-006
    • Clinical Site 48149
• Serbia
  • Beograd, Serbia, 11000
    • Clinical Site 381140
  • Nis, Serbia, 18000
    • Clinical Site 381141
  • Novi Sad, Serbia, 21000
    • Clinical Site 381142
• Singapore
  • Singapore, Singapore, 119074
    • Clinical Site 65127
  • Singapore, Singapore, 169608
    • Clinical Site 65126
• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08003
      • Clinical Site 34155
    • Barcelona, Cataluña, Spain, 08035
      • Clinical Site 34157
    • L'Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Clinical Site 34151
• Sweden
  • Malmo, Sweden
    • Clinical Site 46161
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Clinical Site 1020
  • California
    • Loma Linda, California, United States, 92354
      • Clinical Site 1031
    • Los Angeles, California, United States, 90024
      • Clinical Site 1009
    • Sacremento, California, United States, 95817
      • Clinical Site 1022
    • San Diego, California, United States, 92103
      • Clinical Site 1045
    • San Diego, California, United States, 92123
      • Clinical Site 1049
    • San Francisco, California, United States, 94115
      • Clinical Site 1044
  • Colorado
    • Denver, Colorado, United States, 80220
      • Clinical Site 1011
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Clinical Site 1003
  • Florida
    • Gainesville, Florida, United States, 32610
      • Clinical Site 1036
    • Miami, Florida, United States, 33136
      • Clinical Site 1013
    • Orlando, Florida, United States, 32804
      • Clinical Site 1038
    • Tampa, Florida, United States, 33606
      • Clinical Site 1006
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Clinical Site 1055
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Clinical Site 1053
    • Peoria, Illinois, United States, 61603
      • Clinical Site 1056
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Clinical Site 1026
  • Maine
    • Portland, Maine, United States, 04102
      • Clinical Site 1052
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Clinical Site 1014
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Clinical Site 1018
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Clinical Site 1048
    • Livingston, New Jersey, United States, 07039
      • Clinical Site 1037
    • New Brunswick, New Jersey, United States, 08901
      • Clinical Site 1033
  • New York
    • Albany, New York, United States, 12208
      • Clinical Site 1060
    • Bronx, New York, United States, 10467
      • Clinical Site 1035
    • Buffalo, New York, United States, 14203
      • Clinical Site 1042
    • East Setauket, New York, United States, 11733
      • Clinical Site 1040
    • New York, New York, United States, 10016
      • Clinical Site 1050
    • New York, New York, United States, 10029
      • Clinical Site 1019
    • New York, New York, United States, 10065
      • Clinical Site 1025
    • Valhalla, New York, United States, 10595
      • Clinical Site 1010
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical Site 1051
    • Durham, North Carolina, United States, 27710
      • Clinical Site 1032
    • Greenville, North Carolina, United States, 27834
      • Clinical Site 1058
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Clinical Site 1005
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17105-8700
      • Clinical Site 1054
    • Philadelphia, Pennsylvania, United States, 19102
      • Clinical Site 1023
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Clinical Site 1021
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Clinical Site 1012
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Clinical Site 1047
  • Texas
    • Houston, Texas, United States, 77030
      • Clinical Site 1029
    • San Antonio, Texas, United States, 78215-2035
      • Clinical Site 1061
    • San Antonio, Texas, United States, 78229
      • Clinical Site 1039
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Clinical Site 1027
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Clinical Site 1046
    • Milwaukee, Wisconsin, United States, 53226
      • Clinical Site 1008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: LCP-Tacro; Tacrolimus, once-per-day 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.; Other Names: Tacrolimus modifed-release
Experimental: 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.	Drug: Prograf (tacrolimus); Administered per current product labeling; Other Names: tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Efficacy Endpoint for the Study is the Proportion of Treatment Failures Within 12 Months After Randomization to Study Drug.	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.	360 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	734 days

Collaborators and Investigators

• Sponsor: Veloxis Pharmaceuticals
• Investigators: Study Director: Alan Glicklich, VP, Clinical Operations

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: August 23, 2010
• First Submitted That Met QC Criteria: August 23, 2010
• First Posted (Estimate): August 24, 2010

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Tacrolimus; Kidney; Acute 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-3002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No