Pharmacokinetics of Generic to Brand Tacrolimus in Stable Renal Transplant Patients

Novartis

Status and phase: Completed; Phase 4

Conditions: Renal Transplant

Treatments: Drug: Generic Tacrolimus; Drug: Branded Tacrolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT01256294

CERL080AUS90

Details and patient eligibility

About

The study is designed to compare the pharmacokinetics of generic tacrolimus (Sandoz) to branded tacrolimus (Prograf) in stable renal transplant patients.

Enrollment: 71 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to participate and willing to give written informed consent and to comply with the study visits and restrictions.
• Patient who has received a primary or secondary kidney transplant
• Patient who is at least 6 months post transplant and on a stable dose of tacrolimus as defined by physician, one tacrolimus trough level within the physician defined target range within past 6 months and one additional trough level during the screening period within 30% of the physician defined target range.
• Body mass index (BMI) greater than or equal to 19 but less than or equal to 35
• Patients who are taking tacrolimus (generic, Sandoz) or Prograf

Exclusion criteria

• Evidence of any acute rejection

• Patients who require dialysis within 6 months prior to study entry

• Recipients of antibodies blood group (ABO) incompatible allograft or positive crossmatch

• Recipients of multiple organ transplants

• Patients who have tested positive for hepatitis B surface antigen (HBsAG) or human immunodeficiency virus (HIV), or who are recipients of organ from donors who are known to be HBsAG or HIV positive. Virology screening at the time of transplant was acceptable unless more recent tests were available.

• History of malignancy, treated or untreated, within the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma

• Glomerular filtration rate ≤35 ml/min measured by modification of diet in renal disease (MDRD4)

• No anticipated change in the immunosuppressive regimen during patient participation other than that required by the protocol

• Initiation of any medications that could interfere with tacrolimus blood levels, including over the counter medications, herbal supplements, grapefruit or grapefruit juice.

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are

  • women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
  • women whose partners have been sterilized by vasectomy or other means
  • using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.

• Patients who are taking a generic tacrolimus product other than tacrolimus (generic, Sandoz).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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71 participants in 2 patient groups

Sequence 1 - Branded Tacrolimus / Generic Tacrolimus

Experimental group

Description:

In Period 1 (Days 1-14) participants received branded tacrolimus (Prograf) orally twice a day and in Period 2 (Days 15 - 28) participants received generic tacrolimus (Sandoz) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).

Treatment:

Drug: Branded Tacrolimus

Drug: Generic Tacrolimus

Sequence 2 - Generic Tacrolimus / Branded Tacrolimus

Active Comparator group

Description:

In Period 1 (Days 1 - 14) participants received generic tacrolimus (Sandoz) orally twice a day and in Period 2 (Days 15 - 28) participants received branded tacrolimus (Prograf) orally twice a day. Participants received the same stable dosage of tacrolimus they had been taking prior to enrollment (on a milligram for milligram basis).

Treatment:

Drug: Branded Tacrolimus

Drug: Generic Tacrolimus