Clinical trial NCT01187953: Double-Blind,Double-Dummy,Efficacy/Safety,LCP-Tacro™ Vs Prograf®,Prevention Rejection,De Novo Adult Kidney Tx
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Renal Failure
Keywords: Tacrolimus
Acute Rejection
Kidney
Lead sponsor: Veloxis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-08-24
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: The Primary Efficacy Endpoint for the Study is the Proportion of Treatment Failures Within 12 Months After Randomization to Study Drug.
timeFrame: 360 days
Secondary outcomes:
measure: 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.
timeFrame: 734 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Site 1020
state: Alabama
city: Loma Linda
country: United States
facility: Clinical Site 1031
state: California
city: Los Angeles
country: United States
facility: Clinical Site 1009
state: California
city: Sacremento
country: United States
facility: Clinical Site 1022
state: California
city: San Diego
country: United States
facility: Clinical Site 1045
state: California
city: San Diego
country: United States
facility: Clinical Site 1049
state: California
city: San Francisco
country: United States
facility: Clinical Site 1044
state: California
city: Denver
country: United States
facility: Clinical Site 1011
state: Colorado
city: New Haven
country: United States
facility: Clinical Site 1003
state: Connecticut
city: Gainesville
country: United States
facility: Clinical Site 1036
state: Florida
city: Miami
country: United States
facility: Clinical Site 1013
state: Florida
city: Orlando
country: United States
facility: Clinical Site 1038
state: Florida
city: Tampa
country: United States
facility: Clinical Site 1006
state: Florida
city: Atlanta
country: United States
facility: Clinical Site 1055
state: Georgia
city: Chicago
country: United States
facility: Clinical Site 1053
state: Illinois
city: Peoria
country: United States
facility: Clinical Site 1056
state: Illinois
city: New Orleans
country: United States
facility: Clinical Site 1026
state: Louisiana
city: Portland
country: United States
facility: Clinical Site 1052
state: Maine
city: Boston
country: United States
facility: Clinical Site 1014
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Site 1018
state: Michigan
city: Hackensack
country: United States
facility: Clinical Site 1048
state: New Jersey
city: Livingston
country: United States
facility: Clinical Site 1037
state: New Jersey
city: New Brunswick
country: United States
facility: Clinical Site 1033
state: New Jersey
city: Albany
country: United States
facility: Clinical Site 1060
state: New York
city: Bronx
country: United States
facility: Clinical Site 1035
state: New York
city: Buffalo
country: United States
facility: Clinical Site 1042
state: New York
city: East Setauket
country: United States
facility: Clinical Site 1040
state: New York
city: New York
country: United States
facility: Clinical Site 1050
state: New York
city: New York
country: United States
facility: Clinical Site 1019
state: New York
city: New York
country: United States
facility: Clinical Site 1025
state: New York
city: Valhalla
country: United States
facility: Clinical Site 1010
state: New York
city: Chapel Hill
country: United States
facility: Clinical Site 1051
state: North Carolina
city: Durham
country: United States
facility: Clinical Site 1032
state: North Carolina
city: Greenville
country: United States
facility: Clinical Site 1058
state: North Carolina
city: Cleveland
country: United States
facility: Clinical Site 1005
state: Ohio
city: Harrisburg
country: United States
facility: Clinical Site 1054
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Site 1023
state: Pennsylvania
city: Providence
country: United States
facility: Clinical Site 1021
state: Rhode Island
city: Charleston
country: United States
facility: Clinical Site 1012
state: South Carolina
city: Nashville
country: United States
facility: Clinical Site 1047
state: Tennessee
city: Houston
country: United States
facility: Clinical Site 1029
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 1061
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 1039
state: Texas
city: Richmond
country: United States
facility: Clinical Site 1027
state: Virginia
city: Madison
country: United States
facility: Clinical Site 1046
state: Wisconsin
city: Milwaukee
country: United States
facility: Clinical Site 1008
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Clinical Site 54163
city: Cordoba
country: Argentina
facility: Clinical Site 54164
city: Camperdown
country: Australia
facility: Clinical Site 61101
state: New South Wales
city: Woodville
country: Australia
facility: Clinical Site 61105
state: South Australia
city: Clayton
country: Australia
facility: Clinical Site 61100
state: Victoria
city: Parkville
country: Australia
facility: Clinical Site 61104
state: Victoria
city: Nedlands
country: Australia
facility: Clinical Site 61102
state: Western Australia
city: Perth
country: Australia
facility: Clinical Site 61106
state: Western Australia
city: Juiz de Fora
country: Brazil
facility: Clinical Site 55178
city: Porto Alegre, Rio Grande do Sul
country: Brazil
facility: Clinical Site 55172
city: Porto Alegre, Rio Grande do Sul
country: Brazil
facility: Clinical Site 55179
city: Ribeirao Preto
country: Brazil
facility: Clinical Site 55175
city: Rio de Janeiro
country: Brazil
facility: Clinical Site 55173
city: Sao Paulo
country: Brazil
facility: Clinical Site 55171
city: Brest
country: France
facility: Clinical Site 33132
city: Nice
country: France
facility: Clinical Site 33131
city: Saint Etienne
country: France
facility: Clinical Site 33136
city: Toulouse
country: France
facility: Clinical Site 33134
city: Berlin
country: Germany
facility: Clinical Site 49137
city: Essen
country: Germany
facility: Clinical Site 49139
city: Roma
country: Italy
facility: Clinical Site 39144
city: Seoul
country: Korea, Republic of
facility: Clinical Site 92113
city: Aguascalientes
country: Mexico
facility: Clinical Site 52184
city: Cuernavaca, MOR
country: Mexico
facility: Clinical Site 52181
city: Mexico City
country: Mexico
facility: Clinical Site 52183
city: Mexico City
country: Mexico
facility: Clinical Site 52182
city: Auckland
country: New Zealand
facility: Clinical Site 64112
city: Wellington South
country: New Zealand
facility: Clinical Site 64121
city: Bydgoszcz
country: Poland
facility: Clinical Site 48151
city: Szczecin
country: Poland
facility: Clinical Site 48148
city: Warszawa
country: Poland
facility: Clinical Site 48149
city: Beograd
country: Serbia
facility: Clinical Site 381140
city: Nis
country: Serbia
facility: Clinical Site 381141
city: Novi Sad
country: Serbia
facility: Clinical Site 381142
city: Singapore
country: Singapore
facility: Clinical Site 65127
city: Singapore
country: Singapore
facility: Clinical Site 65126
city: Barcelona
country: Spain
facility: Clinical Site 34155
state: Cataluña
city: Barcelona
country: Spain
facility: Clinical Site 34157
state: Cataluña
city: L'Hospitalet de Llobregat
country: Spain
facility: Clinical Site 34151
state: Cataluña
city: Malmo
country: Sweden
facility: Clinical Site 46161
Study officials:
affiliation: VP, Clinical Operations
name: Alan Glicklich
role: STUDY_DIRECTOR
References: