Pharmacokinetic Studies of Tacrolimus in Transplant Patients

• Status: Completed
• Trial end date: 2016-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The study is designed to compare the steady-state pharmacokinetics of Prograf (Brand) and the two most disparate generic formulations (Generic Hi and Generic Lo) in a fully replicated, 3-way cross-over study in stable kidney (n=36) and liver transplant (n=36) subjects.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Cincinnati
• Collaborators: Children's Hospital Medical Center, Cincinnati; University of Colorado, Denver
• Treatments: Tacrolimus

Criteria

Inclusion Criteria:

1. ≥18 years old, male or female

2. Able to participate and willing to give written informed consent and to comply with the study visits and restrictions.

3. Subject who has received a primary or secondary kidney or liver transplant.

4. Subject 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.

5. BMI greater than or equal to 19 but less than or equal to 40.

6. Ability to perform daily finger sticks to provide blood sample

Exclusion Criteria:

1. Evidence of any acute rejection

2. Subjects who require dialysis within 6 months prior to study entry

3. Recipients of multiple organ transplants

4. Subjects who have tested positive for HBsAG or 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.

5. Hep C positive subjects with liver biopsy proven recurrent disease considered relevant by physician oversight.

6. Subjects with any severe medical condition requiring acute or chronic treatment that in the investigator's opinion would interfere with study participation

7. History of malignancy, treated or untreated, with the past 2 years with the exception of carcinoma in situ or excised basal cell carcinoma, or hepatocellular carcinoma prior to transplant.

8. GFR ≤ 35 ml/min measured as estimated using the MDRD4 formula

9. Subjects with aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin ≥ 3 X upper limit of normal (ULN) or other evidence of severe liver disease

10. Subjects with white blood cell (WBC) count ≤2,000/ mm3 or with thrombocytopenia (platelet count ≤ 75,000/ mm3), with an absolute neutrophil count of ≤ 1,500/ mm3 or hemoglobin <8g/dL)

11. Subjects with clinically significant infections, requiring therapy, which, in the investigator's opinion, would interfere with the objectives of the study

12. Other mental or physical conditions which in the investigator's opinion, are considered clinically significant

13. Presence of intractable immunosuppressant complications or side effects resulting in dose adjustment of tacrolimus

14. Subjects who have been exposed to an investigational therapy within 30 days prior to enrollment or 5 half-lives of the investigational product, whichever is greater.

15. An anticipated change in the immunosuppressive regimen during subject participation other than that required by the protocol

16. Subject with severe GI disturbance or diarrhea which could interfere with tacrolimus absorption

17. Severe diabetic gastroparesis

18. Initiation of any medications that could interfere with tacrolimus blood levels, including OTC medications, herbal supplements, grapefruit or grapefruit juice.

19. 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 beta human chorionic gonadotrophin (BhCG) laboratory test (> 5 mIU/mL)

20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are

1. women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner; women whose partners have been sterilized by vasectomy or

2. 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.