Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients

NCT02866682 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 14-001423
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

As the patents for brand-name immunosuppressive medications expire, there is increasing interest in using generic immunosuppressive drugs. However, despite pharmacokinetic studies showing bioequivalence, questions remain regarding the clinical impact of use of generic immunosuppression. The most important immunosuppressive agent in the modern transplant era is arguably tacrolimus, a calcineurin-inhibitor with a narrow therapeutic index. This study seeks to answer the question regarding the clinical impact of generic tacrolimus use as measured primarily by acute rejection, loss of graft function, and patient death through a randomized trial of 2 phases: Brand tacrolimus only, and Generic A tacrolimus only. Given that kidney transplantations are the most commonly performed transplants with well-defined measures of rejection and graft failure, this organs will be studied in a six-center study designed to accrue the target number of transplant recipients within the one-year study period. The study has now been branched off into 2 phases. Phase 1: consists of randomization of patients onto brand and generic tacrolimus. This was completed once 40 brand patients were enrolled. Phase 2: consists of patients being enrolled only on generic tacrolimus (standard of care from subject's insurance). This will be completed once there is a total of 160 generic participants. 200 participants total in the study.

Conditions

Renal Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Time to First Occurrence of Acute Rejection, Failure, Death

  The definition of graft failure includes re-transplant and/or death and, in case of kidney transplant, also includes return to dialysis. Acute rejection was defined as biopsy-proven rejection according to Banff 2007 criteria. Please see the following article for details of the Banff '07 classification: https://www.sciencedirect.com/science/article/pii/S1600613522056428?via%3Dihub.

  1 year post-transplant

Secondary Outcomes (9)

• Number of Participants With Graft Rejection at 1 Year

  1 year post-transplant

• Number of Participants With Graft Failure at 1 Year

  1 year post-transplant

• Number of Participants With Infectious Episodes at 1 Year

  1 year post-transplant

• Number of Participants With Malignancy at 1 Year

  1 year post-transplant

• Death or Loss-to-follow-up at 1 Year

  1 year post-transplant

Study Arms (2)

Brand Tacrolimus Only : Prograf

OTHER

Arm 1 will receive brand tacrolimus for the entire study

Drug: Prograf

Generic A Only

OTHER

Arm 2 will receive specific generic tacrolimus for the entire study

Drug: Tacrolimus

Interventions

Prograf DRUG

Brand Drug for the duration of the study.

Brand Tacrolimus Only : Prograf

Tacrolimus DRUG

Generic

Generic A Only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and or/assent
• Between the ages of 18 and 70 years, inclusive
• Able to swallow tablets and capsules at the time of randomization
• Subjects must be receiving a primary or secondary kidney allograft from a deceased donor or from a non- HLA identical living donor
• Negative cross match test, and compatible (A, B, AB or O) blood type
• Subjects must have no known contraindications to tacrolimus
• Women of childbearing potential (WOCBP) must have a negative pregnancy test and be willing to use 2 methods of contraception during the study and for 6 weeks after stopping the study drug.
• WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level \> 35 mIU/cc). Women who are using oral, implanted, or injectable contraceptive hormones (intrauterine device), mechanical products or barrier methods (diaphragm, condoms, spermicides), are practicing abstinence, or have a sterile partner (e.g., vasectomy), will be considered of child bearing potential.
• In addition, WOCBP who are taking MMF must use methods of birth control as stipulated in the package insert, namely:
• Either intrauterine device, or partner with vasectomy, or one hormone (oral contraceptive pill, transdermal patch, vaginal ring, or progesterone injection or implant) and one barrier method (diaphragm or cervical cap with spermicide, contraceptive sponge, or male or female condom), or two barrier methods as described above.
• WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) at the time of transplant.

You may not qualify if:

• Those who receive simultaneous combined organ transplants
• Subjects with clinically significant active infections (for example, those requiring hospitalization, or as judged by the Investigator) or malignancies
• Recipients who are concurrently receiving belatacept or anticipate to receive belatacept as part of their immunosuppressive regimen
• Subjects currently enrolled in another investigational device or drug study
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for 6 weeks after stopping the study drug
• Women who are breast-feeding or pregnant with a positive pregnancy test on enrollment or prior to study drug administration
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
• Any psychiatric or medical condition that, in the investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

UCLA Kidney Transplant Research

Los Angeles, California, 90024, United States

Location

Related Publications (1)

• Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2.

  PMID: 36094829 DERIVED

MeSH Terms

Interventions

Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Suphamai Bunnapradist
• Organization: University of California, Los Angeles (UCLA)

bunnapradist@mednet.ucla.edu

310-794-8516

Study Officials

• Suphamai Bunnapradist, M.D.,M.S.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Director of Research

Study Record Dates

• First Submitted: July 26, 2016
• First Posted: August 15, 2016
• Study Start: March 1, 2018
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: April 28, 2023
• Results First Posted: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)