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

NCT ID: NCT01187953

Last Updated: 2016-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 543 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2014-03-31

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.

Conditions

Renal Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

LCP-Tacro

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Prograf (tacrolimus)

Intervention Type: DRUG

Administered per current product labeling

Interventions

Prograf (tacrolimus)

Administered per current product labeling

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

tacrolimus; Tacrolimus modifed-release

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Veloxis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan Glicklich

Role: STUDY_DIRECTOR

VP, Clinical Operations

Locations

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

Clinical Site 1013

Miami, Florida, United States

Clinical Site 1038

Orlando, Florida, United States

Clinical Site 1006

Tampa, Florida, United States

Clinical Site 1055

Atlanta, Georgia, United States

Clinical Site 1053

Chicago, Illinois, United States

Clinical Site 1056

Peoria, Illinois, United States

Clinical Site 1026

New Orleans, Louisiana, United States

Clinical Site 1052

Portland, Maine, United States

Clinical Site 1014

Boston, Massachusetts, United States

Clinical Site 1018

Detroit, Michigan, United States

Clinical Site 1048

Hackensack, New Jersey, United States

Clinical Site 1037

Livingston, New Jersey, United States

Clinical Site 1033

New Brunswick, New Jersey, United States

Clinical Site 1060

Albany, New York, United States

Clinical Site 1042

Buffalo, New York, United States

Clinical Site 1040

East Setauket, New York, United States

Clinical Site 1050

New York, New York, United States

Clinical Site 1019

New York, New York, United States

Clinical Site 1025

New York, New York, United States

Clinical Site 1035

The Bronx, New York, United States

Clinical Site 1010

Valhalla, New York, United States

Clinical Site 1051

Chapel Hill, North Carolina, United States

Clinical Site 1032

Durham, North Carolina, United States

Clinical Site 1058

Greenville, North Carolina, United States

Clinical Site 1005

Cleveland, Ohio, United States

Clinical Site 1054

Harrisburg, Pennsylvania, United States

Clinical Site 1023

Philadelphia, Pennsylvania, United States

Clinical Site 1021

Providence, Rhode Island, United States

Clinical Site 1012

Charleston, South Carolina, United States

Clinical Site 1047

Nashville, Tennessee, United States

Clinical Site 1029

Houston, Texas, United States

Clinical Site 1061

San Antonio, Texas, United States

Clinical Site 1039

San Antonio, Texas, United States

Clinical Site 1027

Richmond, Virginia, United States

Clinical Site 1046

Madison, Wisconsin, United States

Clinical Site 1008

Milwaukee, Wisconsin, United States

Clinical Site 54163

Buenos Aires, , Argentina

Clinical Site 54164

Córdoba, , Argentina

Clinical Site 61101

Camperdown, New South Wales, Australia

Clinical Site 61105

Woodville, South Australia, Australia

Clinical Site 61100

Clayton, Victoria, Australia

Clinical Site 61104

Parkville, Victoria, Australia

Clinical Site 61102

Nedlands, Western Australia, Australia

Clinical Site 61106

Perth, Western Australia, Australia

Clinical Site 55178

Juiz de Fora, , Brazil

Clinical Site 55172

Porto Alegre, Rio Grande Do Sul, , Brazil

Clinical Site 55179

Porto Alegre, Rio Grande Do Sul, , Brazil

Clinical Site 55175

Ribeirão Preto, , Brazil

Clinical Site 55173

Rio de Janeiro, , Brazil

Clinical Site 55171

São Paulo, , Brazil

Clinical Site 33132

Brest, , France

Clinical Site 33131

Nice, , France

Clinical Site 33136

Saint-Etienne, , France

Clinical Site 33134

Toulouse, , France

Clinical Site 49137

Berlin, , Germany

Clinical Site 49139

Essen, , Germany

Clinical Site 39144

Roma, , Italy

Clinical Site 52184

Aguascalientes, , Mexico

Clinical Site 52181

Cuernavaca, MOR, , Mexico

Clinical Site 52183

Mexico City, , Mexico

Clinical Site 52182

Mexico City, , Mexico

Clinical Site 64112

Auckland, , New Zealand

Clinical Site 64121

Wellington South, , New Zealand

Clinical Site 48151

Bydgoszcz, , Poland

Clinical Site 48148

Szczecin, , Poland

Clinical Site 48149

Warsaw, , Poland

Clinical Site 381140

Belgrade, , Serbia

Clinical Site 381141

Niš, , Serbia

Clinical Site 381142

Novi Sad, , Serbia

Clinical Site 65127

Singapore, , Singapore

Clinical Site 65126

Singapore, , Singapore

Clinical Site 92113

Seoul, , South Korea

Clinical Site 34155

Barcelona, Catalonia, Spain

Clinical Site 34157

Barcelona, Catalonia, Spain

Clinical Site 34151

L'Hospitalet de Llobregat, Catalonia, Spain

Clinical Site 46161

Malmo, , Sweden

Countries

United States; Argentina; Australia; Brazil; France; Germany; Italy; Mexico; New Zealand; Poland; Serbia; Singapore; South Korea; Spain; Sweden

Other Identifiers

LCP-Tacro-3002

Identifier Type: -

Identifier Source: org_study_id