Clinical trial NCT01256294: Pharmacokinetics of Generic to Brand Tacrolimus in Stable Renal Transplant Patients
Official title: A Prospective, Multi-center, Open-label, Randomized, Two Period, Two Sequence, Crossover Study to Compare the Steady State Pharmacokinetics of Generic Tacrolimus (Sandoz) to Prograf in Stable Renal Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant
Keywords: Renal transplant
kidney transplant
immunosuppressive therapy
anti-rejection medication
pharmacokinetics
tacrolimus
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Sandoz
First posted: 2010-12-08
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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).

Primary outcomes:
measure: Dose-Normalized Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) at Steady State
timeFrame: Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.
measure: Dose-normalized Maximum Plasma Drug Concentration (Cmax) at Steady State
timeFrame: Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.
Secondary outcomes:
measure: Intra-patient Variability of Tacrolimus Pharmacokinetic Parameters
timeFrame: Days 7 and 14, and Days 21 and 28.
measure: Trough Plasma Drug Concentration (C0) at Steady State
timeFrame: Days 14 and 28: predose
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: 28 Days
measure: Number of Participants With Reported Biopsy Proven Acute Rejection Episodes
timeFrame: 28 Days
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: