Double-Blind,Double-Dummy,Efficacy/Safety,LCP-Tacro™ Vs Prograf®,Prevention Rejection,De Novo Adult Kidney Tx
- 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
- 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
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Recipients of any non-renal transplant (solid organ or bone marrow) ever
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Panel reactive antibody (PRA) >30%
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Patients with any condition that may affect study drug absorption (e.g. gastrectomy or clinically significant diabetic gastroenteropathy)
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Body mass index (BMI) 18 kg/m2
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History of alcohol abuse
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History of recreational drug abuse
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Screening 12-lead electrocardiogram (ECG) demonstrating clinically relevant abnormalities
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WOCBP who are either pregnant, lactating, planning to become pregnant
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Patients with an oral temperature (prior to study drug dosing) of 38.0 ºC (100.4 ºF) or higher
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Patients with clinically significant active infections
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Patients with a known hereditary immunodeficiency
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Patients with malignancies or with a history of malignancies (within the last 5 years)
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Patients who are receiving or expect to receive sirolimus, everolimus, azathioprine,or cyclophosphamide within 3 months prior to enrollment
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Patients with evidence of clinically significant disease (e.g., cardiac, gastrointestinal or hepatic disorders)
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Patients with reversible cardiac ischemia (history of untreated reversible ischemia on stress test)
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Patients with clinically symptomatic congestive heart failure or documented ejection fraction of less than 45%
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Patients with significant chronic obstructive pulmonary disease, pulmonary restrictive disease or significant pulmonary hypertension
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Treatment with an investigational drug, device or regimen within 1 year preceding the first dose of study drug
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Patients who are unwilling to refrain from consumption of grapefruit or grapefruit containing juices
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Patients receiving concomitant drugs that may affect concentrations of tacrolimus in whole blood, as listed in Appendix 2
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Laboratory variables that are abnormal (outside laboratory reference range) and clinically relevant, as judged by the Investigator
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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).
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Patients who experienced graft loss within 1 year of transplant, due to acute rejection or due to BK nephropathy
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Patients having experienced focal segmental glomerulosclerosis (FSGS)
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Donor with positive serological test result for HIV-1, HBV or HCV
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Donor with history of malignant disease (current or historical)
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Centers for Disease Control and Prevention high-risk donor
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Patients with mental dysfunction or inability to cooperate with the study
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Cold ischemia time >30 hours
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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 1058
🇺🇸Greenville, North Carolina, United States
Clinical Site 1023
🇺🇸Philadelphia, Pennsylvania, United States
Clinical Site 1003
🇺🇸New Haven, Connecticut, United States
Clinical Site 1037
🇺🇸Livingston, New Jersey, United States
Clinical Site 1012
🇺🇸Charleston, South Carolina, United States
Clinical Site 61104
🇦🇺Parkville, Victoria, Australia
Clinical Site 54164
🇦🇷Cordoba, Argentina
Clinical Site 52181
🇲🇽Cuernavaca, MOR, Mexico
Clinical Site 48151
🇵🇱Bydgoszcz, Poland
Clinical Site 381142
🇷🇸Novi Sad, Serbia
Clinical Site 65127
🇸🇬Singapore, Singapore
Clinical Site 1014
🇺🇸Boston, Massachusetts, United States
Clinical Site 1029
🇺🇸Houston, Texas, United States
Clinical Site 1031
🇺🇸Loma Linda, California, United States
Clinical Site 1055
🇺🇸Atlanta, Georgia, United States
Clinical Site 1053
🇺🇸Chicago, Illinois, United States
Clinical Site 1049
🇺🇸San Diego, California, United States
Clinical Site 1011
🇺🇸Denver, Colorado, United States
Clinical Site 39144
🇮🇹Roma, Italy
Clinical Site 1010
🇺🇸Valhalla, New York, United States
Clinical Site 1042
🇺🇸Buffalo, New York, United States
Clinical Site 1045
🇺🇸San Diego, California, United States
Clinical Site 1044
🇺🇸San Francisco, California, United States
Clinical Site 1013
🇺🇸Miami, Florida, United States
Clinical Site 1026
🇺🇸New Orleans, Louisiana, United States
Clinical Site 1052
🇺🇸Portland, Maine, United States
Clinical Site 1035
🇺🇸Bronx, New York, United States
Clinical Site 61105
🇦🇺Woodville, South Australia, Australia
Clinical Site 61106
🇦🇺Perth, Western Australia, Australia
Clinical Site 49137
🇩🇪Berlin, Germany
Clinical Site 55175
🇧🇷Ribeirao Preto, Brazil
Clinical Site 1038
🇺🇸Orlando, Florida, United States
Clinical Site 46161
🇸🇪Malmo, Sweden
Clinical Site 1048
🇺🇸Hackensack, New Jersey, United States
Clinical Site 1060
🇺🇸Albany, New York, United States
Clinical Site 55179
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil
Clinical Site 1005
🇺🇸Cleveland, Ohio, United States
Clinical Site 1056
🇺🇸Peoria, Illinois, United States
Clinical Site 49139
🇩🇪Essen, Germany
Clinical Site 34157
🇪🇸Barcelona, Cataluña, Spain
Clinical Site 1050
🇺🇸New York, New York, United States
Clinical Site 1033
🇺🇸New Brunswick, New Jersey, United States
Clinical Site 1018
🇺🇸Detroit, Michigan, United States
Clinical Site 54163
🇦🇷Buenos Aires, Argentina
Clinical Site 52184
🇲🇽Aguascalientes, Mexico
Clinical Site 48148
🇵🇱Szczecin, Poland
Clinical Site 1054
🇺🇸Harrisburg, Pennsylvania, United States
Clinical Site 1032
🇺🇸Durham, North Carolina, United States
Clinical Site 1025
🇺🇸New York, New York, United States
Clinical Site 1061
🇺🇸San Antonio, Texas, United States
Clinical Site 1039
🇺🇸San Antonio, Texas, United States
Clinical Site 1046
🇺🇸Madison, Wisconsin, United States
Clinical Site 61100
🇦🇺Clayton, Victoria, Australia
Clinical Site 33134
🇫🇷Toulouse, France
Clinical Site 55171
🇧🇷Sao Paulo, Brazil
Clinical Site 55173
🇧🇷Rio de Janeiro, Brazil
Clinical Site 52182
🇲🇽Mexico City, Mexico
Clinical Site 48149
🇵🇱Warszawa, Poland
Clinical Site 381141
🇷🇸Nis, Serbia
Clinical Site 65126
🇸🇬Singapore, Singapore
Clinical Site 55178
🇧🇷Juiz de Fora, Brazil
Clinical Site 64112
🇳🇿Auckland, New Zealand
Clinical Site 52183
🇲🇽Mexico City, Mexico
Clinical Site 381140
🇷🇸Beograd, Serbia
Clinical Site 64121
🇳🇿Wellington South, New Zealand
Clinical Site 61102
🇦🇺Nedlands, Western Australia, Australia
Clinical Site 1020
🇺🇸Birmingham, Alabama, United States
Clinical Site 1009
🇺🇸Los Angeles, California, United States
Clinical Site 1022
🇺🇸Sacremento, California, United States
Clinical Site 1036
🇺🇸Gainesville, Florida, United States
Clinical Site 1006
🇺🇸Tampa, Florida, United States
Clinical Site 1040
🇺🇸East Setauket, New York, United States
Clinical Site 1019
🇺🇸New York, New York, United States
Clinical Site 1051
🇺🇸Chapel Hill, North Carolina, United States
Clinical Site 1021
🇺🇸Providence, Rhode Island, United States
Clinical Site 1008
🇺🇸Milwaukee, Wisconsin, United States
Clinical Site 1027
🇺🇸Richmond, Virginia, United States
Clinical Site 61101
🇦🇺Camperdown, New South Wales, Australia
Clinical Site 55172
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil
Clinical Site 33136
🇫🇷Saint Etienne, France
Clinical Site 33132
🇫🇷Brest, France
Clinical Site 33131
🇫🇷Nice, France
Clinical Site 34151
🇪🇸L'Hospitalet de Llobregat, Cataluña, Spain
Clinical Site 34155
🇪🇸Barcelona, Cataluña, Spain
Clinical Site 92113
🇰🇷Seoul, Korea, Republic of
Clinical Site 1047
🇺🇸Nashville, Tennessee, United States