Pharmacokinetics of Generic to Brand Tacrolimus in Stable Renal Transplant Patients

Renal Transplant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01256294
• Other study ID #: CERL080AUS90
• Status: Completed
• Phase: Phase 4
• First received: November 1, 2010
• Last updated: May 21, 2012
• Start date: October 2010
• Est. completion date: May 2011

Study information

• Verified date: May 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplant

Intervention

Drug:
• Generic Tacrolimus
Generic Sandoz tacrolimus supplied as capsules of 0.5 mg, 1 mg and 5 mg dose strengths.
• Branded Tacrolimus
Capsules supplied at dose strengths of 0.5 mg, 1 mg, and 5 mg.

Locations

Country	Name	City	State
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Sandoz

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Normalized Area Under the Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) at Steady State	Dose-normalized area under the concentration-time curve from time 0 to 12 hours (AUC0-12h) at steady state after 14 days of treatment with each study drug.; Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.	Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.	No
Primary	Dose-normalized Maximum Plasma Drug Concentration (Cmax) at Steady State	Maximum (peak) plasma drug concentration after drug administration at steady state (after 14 days of treatment with each study drug). Geometric mean and 95% confidence intervals were determined from an analysis of variance (ANOVA) model for the dose-normalized log transformed values with treatment, period and sequence as fixed factors and patients nested within sequences as a random factor.	Days 14 and 28: Predose and at 0.5, 1, 1.5, 1.75, 2, 3, 4, 8 and 12 hours after dosing.	No
Secondary	Intra-patient Variability of Tacrolimus Pharmacokinetic Parameters	The intra-patient variability of tacrolimus pharmacokinetics of each formulation was evaluated by comparing AUC0-12h, maximum drug concentration (Cmax) and trough drug concentration (C0) at Days 7 and 14, and Days 21 and 28. Intra-patient variability was assessed by a calculation of the coefficient of variation, by patient, using the repeated measurements within each Period, where the coefficient of variation (%) = standard deviation/mean*100.	Days 7 and 14, and Days 21 and 28.	No
Secondary	Trough Plasma Drug Concentration (C0) at Steady State	Trough plasma drug concentration measured prior to drug administration at steady state (after 14 days of treatment with each study drug).	Days 14 and 28: predose	No
Secondary	Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)	An AE was defined as the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event was not considered to be related to study drug. An SAE was an event which: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; required or prolonged inpatient hospitalization; was medically significant, i.e., an event that jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.	28 Days	No
Secondary	Number of Participants With Reported Biopsy Proven Acute Rejection Episodes		28 Days	No