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

Renal Failure Clinical Trial

— LCPTacro3002  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01187953
• Other study ID #: LCP-Tacro-3002
• Status: Completed
• Phase: Phase 3
• First received: August 23, 2010
• Last updated: May 12, 2015
• Start date: September 2010
• Est. completion date: March 2014

Study information

• Verified date: May 2015
• Source: Veloxis Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 543
• Est. completion date: March 2014
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Renal Failure

Intervention

Drug:
• Prograf (tacrolimus)
Administered per current product labeling
• 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.

Locations

Country	Name	City	State
Argentina	Clinical Site 54163	Buenos Aires
Argentina	Clinical Site 54164	Cordoba
Australia	Clinical Site 61101	Camperdown	New South Wales
Australia	Clinical Site 61100	Clayton	Victoria
Australia	Clinical Site 61102	Nedlands	Western Australia
Australia	Clinical Site 61104	Parkville	Victoria
Australia	Clinical Site 61106	Perth	Western Australia
Australia	Clinical Site 61105	Woodville	South Australia
Brazil	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	Ribeirao Preto
Brazil	Clinical Site 55173	Rio de Janeiro
Brazil	Clinical Site 55171	Sao Paulo
France	Clinical Site 33132	Brest
France	Clinical Site 33131	Nice
France	Clinical Site 33136	Saint Etienne
France	Clinical Site 33134	Toulouse
Germany	Clinical Site 49137	Berlin
Germany	Clinical Site 49139	Essen
Italy	Clinical Site 39144	Roma
Korea, Republic of	Clinical Site 92113	Seoul
Mexico	Clinical Site 52184	Aguascalientes
Mexico	Clinical Site 52181	Cuernavaca, MOR
Mexico	Clinical Site 52182	Mexico City
Mexico	Clinical Site 52183	Mexico City
New Zealand	Clinical Site 64112	Auckland
New Zealand	Clinical Site 64121	Wellington South
Poland	Clinical Site 48151	Bydgoszcz
Poland	Clinical Site 48148	Szczecin
Poland	Clinical Site 48149	Warszawa
Serbia	Clinical Site 381140	Beograd
Serbia	Clinical Site 381141	Nis
Serbia	Clinical Site 381142	Novi Sad
Singapore	Clinical Site 65126	Singapore
Singapore	Clinical Site 65127	Singapore
Spain	Clinical Site 34155	Barcelona	Cataluña
Spain	Clinical Site 34157	Barcelona	Cataluña
Spain	Clinical Site 34151	L'Hospitalet de Llobregat	Cataluña
Sweden	Clinical Site 46161	Malmo
United States	Clinical Site 1060	Albany	New York
United States	Clinical Site 1055	Atlanta	Georgia
United States	Clinical Site 1020	Birmingham	Alabama
United States	Clinical Site 1014	Boston	Massachusetts
United States	Clinical Site 1035	Bronx	New York
United States	Clinical Site 1042	Buffalo	New York
United States	Clinical Site 1051	Chapel Hill	North Carolina
United States	Clinical Site 1012	Charleston	South Carolina
United States	Clinical Site 1053	Chicago	Illinois
United States	Clinical Site 1005	Cleveland	Ohio
United States	Clinical Site 1011	Denver	Colorado
United States	Clinical Site 1018	Detroit	Michigan
United States	Clinical Site 1032	Durham	North Carolina
United States	Clinical Site 1040	East Setauket	New York
United States	Clinical Site 1036	Gainesville	Florida
United States	Clinical Site 1058	Greenville	North Carolina
United States	Clinical Site 1048	Hackensack	New Jersey
United States	Clinical Site 1054	Harrisburg	Pennsylvania
United States	Clinical Site 1029	Houston	Texas
United States	Clinical Site 1037	Livingston	New Jersey
United States	Clinical Site 1031	Loma Linda	California
United States	Clinical Site 1009	Los Angeles	California
United States	Clinical Site 1046	Madison	Wisconsin
United States	Clinical Site 1013	Miami	Florida
United States	Clinical Site 1008	Milwaukee	Wisconsin
United States	Clinical Site 1047	Nashville	Tennessee
United States	Clinical Site 1033	New Brunswick	New Jersey
United States	Clinical Site 1003	New Haven	Connecticut
United States	Clinical Site 1026	New Orleans	Louisiana
United States	Clinical Site 1019	New York	New York
United States	Clinical Site 1025	New York	New York
United States	Clinical Site 1050	New York	New York
United States	Clinical Site 1038	Orlando	Florida
United States	Clinical Site 1056	Peoria	Illinois
United States	Clinical Site 1023	Philadelphia	Pennsylvania
United States	Clinical Site 1052	Portland	Maine
United States	Clinical Site 1021	Providence	Rhode Island
United States	Clinical Site 1027	Richmond	Virginia
United States	Clinical Site 1022	Sacremento	California
United States	Clinical Site 1039	San Antonio	Texas
United States	Clinical Site 1061	San Antonio	Texas
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 1006	Tampa	Florida
United States	Clinical Site 1010	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Veloxis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  France,  Germany,  Italy,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Serbia,  Singapore,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No